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Advancing Renal TRANSplant eFficacy and Safety Outcomes With an eveRolimus-based regiMen (TRANSFORM)

Sponsor
Novartis Pharmaceuticals (Industry)
Overall Status
Completed
CT.gov ID
NCT01950819
Collaborator
(none)
2,037
Enrollment
184
Locations
2
Arms
49.5
Actual Duration (Months)
11.1
Patients Per Site
0.2
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is a 2-year, randomized, multicenter, open-label, 2-arm study evaluating the graft function of everolimus and reduced CNI versus MPA and standard CNI in adult de novo renal transplant recipients.

Condition or Disease Intervention/Treatment Phase
Phase 4

Study Design

Study Type:
Interventional
Actual Enrollment :
2037 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Intervention Model Description:
Open-label studyOpen-label study
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A 24 Month, Multicenter, Randomized, Open-label Safety and Efficacy Study of Concentration-controlled Everolimus With Reduced Calcineurin Inhibitor vs Mycophenolate With Standard Calcineurin Inhibitor in de Novo Renal Transplantation
Actual Study Start Date :
Dec 3, 2013
Actual Primary Completion Date :
Feb 1, 2017
Actual Study Completion Date :
Jan 17, 2018

Arms and Interventions

Arm Intervention/Treatment
Experimental: EVR+rCNI

Everolimus with reduced calcineurin inhibitor- everolimus (target trough level of 3-8 ng/mL) in combination with reduced exposure to CNI (cyclosporine or tacrolimus)

Biological: Induction therapy
All subjects received induction therapy with basiliximab or rabbit anti-thymocyte globulin, in the peritransplant period.
Other Names:
  • Simulect, basiliximab, rATG, Thymoglobulin

    • Drug: Corticosteroids
    All subjects received maintenance therapy with corticosteroids throughout the 24 month study period. A minimum dose of 5 mg prednisone, or equivalent, per day was maintained.
    Other Names:
  • prednisone, methylprednisone, methylprednisolone, etc.

    • Drug: EVR+rCNI
    Everolimus with reduced calcineurin inhibitor- everolimus (target trough level of 3-8 ng/mL) in combination with reduced exposure to CNI (cyclosporine or tacrolimus)
    Other Names:
  • Zortress, Certican, Neoral, Prograf

    		•
    Active Comparator: MPA+sCNI

    Mycophenolate (mycophenolic acid sodium or mycophenolate mofetil) in combination with standard exposure to calcineurin inhibitor (cyclosporine or tacrolimus).

    Biological: Induction therapy
    All subjects received induction therapy with basiliximab or rabbit anti-thymocyte globulin, in the peritransplant period.
    Other Names:
  • Simulect, basiliximab, rATG, Thymoglobulin

    • Drug: Corticosteroids
    All subjects received maintenance therapy with corticosteroids throughout the 24 month study period. A minimum dose of 5 mg prednisone, or equivalent, per day was maintained.
    Other Names:
  • prednisone, methylprednisone, methylprednisolone, etc.

    • Drug: MPA+sCNI
    Mycophenolate (mycophenolic acid sodium or mycophenolate mofetil) in combination with standard exposure to calcineurin inhibitor (cyclosporine or tacrolimus).
    Other Names:
  • Myfortic, Cellcept, Neoral, Prograf

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Incidence of Failure on the Composite of Treated Biopsy-proven Acute Rejection (tBPAR) or Estimated Glomerular Filtration Rate (eGFR) < 50 mL/Min/1.73m2. [Month 12 is Primary, Month 24 secondary]

      Incidence of failure on the composite of treated biopsy-proven acute rejection (tBPAR) or estimated glomerular filtration rate (eGFR) < 50 mL/min/1.73m2.

    Secondary Outcome Measures

    1. Incidence of Failure on the Composite of (Treated Biopsy Proven Acute Rejection (tBPAR), Graft Loss or Death [Month 12 and 24]

      Incidence of failure on the composite of (treated biopsy proven acute rejection (tBPAR), graft loss or death

    2. Incidence of Failure on the Composite Endpoint of tBPAR, Graft Loss, Death or eGFR < 50 mL/Min/1.73m2 [Month 12 and 24]

      Incidence of failure on the composite endpoint of tBPAR, graft loss, death or eGFR < 50 mL/min/1.73m2

    3. Incidence of Failure on the Composite Endpoint of Graft Loss or Death. [Month 12 and 24]

      Incidence of failure on the composite endpoint of graft loss or death.

    4. Incidence of Death, Graft Loss, tBPAR, BPAR, tAR, AR and Humoral Rejection [Month 12 and 24]

      Incidence of death, graft loss, tBPAR (treated biopsy proven acute rejection), BPAR (biopsy proven acute rejection), tAR (treated acute rejection), AR (acute rejection) and humoral rejection (aAMR : active antibody mediated rejection and cAMR: chronic antibody mediated rejection)

    5. Incidence of eGFR < 50 mL/Min/1.73m2 [Month 12 and 24]

      Incidence of eGFR < 50 mL/min/1.73m2

    6. Renal Allograft Function : Mean Estimated Glomerular Filtration Rate, eGFR [Baseline (week 4), Month 12 and 24]

      Renal allograft function : mean estimated glomerular filtration rate, eGFR

    7. Evolution of Renal Function, as eGFR, Over Time by Slope Analysis. [Month 12 and 24]

      Rate of change of renal function, as eGFR, calculated using MDRD4 formula (Coresh, 2003) and adjusted by covariates.

    8. Renal Function Assessed by Creatinine Lab Values [Month 12 and 24]

      Mean Renal function as assessed in clinical practice, by ceatinine values. Analysis is done without considering missing values for analysis.

    9. Renal Function by Alternative Formulae (e.g. CKD-EPI). eGFR Values Reported [Month 12 and 24]

      Mean Renal function as used in clinical practice, using different formula for calculation of renal function than MDRD4 (our primary efficacy parameter), and other alternate formulae (e.g. CKD-EPI). Analysis is done without considering missing values for analysis.

    10. Incidence of Adverse Events, Serious Adverse Events and Adverse Events Leading to Study Regimen Discontinuation. [Month 24]

      Incidence of adverse events, serious adverse events and adverse events leading to study regimen discontinuation.

    11. Incidence of Cytomegalovirus and BK Virus, New Onset Diabetes Mellitus, Chronic Kidney Disease With Associated Proteinuria and Calcineurin Inhibitor Associated Adverse Events. [Month 24]

      Incidence of cytomegalovirus and BK virus, new onset diabetes mellitus, chronic kidney disease with associated proteinuria and calcineurin inhibitor associated adverse events.

    12. Urinary Protein and Albumin Excretion by Treatment Estimated by Urinary Protein/Creatinine and Urinary Albumin/Creatinine Ratios. [Baseline, Month 12 and 24]

      Mean urinary protein and albumin excretion by treatment estimated by mean urinary protein/creatinine and urinary albumin/creatinine ratios.

    13. Incidence of Major Cardiovascular Events. [Month 24]

      Incidence of major cardiovascular events by Preferred Term

    14. Incidence of Malignancies. [Month 24]

      Incidence of malignancies.

    15. Incidence of Failure on the Composite of Treated Biopsy-proven Acute Rejection (tBPAR) or Estimated Glomerular Filtration Rate (eGFR) < 50 mL/Min/1.73m2 Among Compliant Subjects. [Month 12 and 24]

      Incidence of failure on the composite of treated biopsy-proven acute rejection (tBPAR) or estimated glomerular filtration rate (eGFR) < 50 mL/min/1.73m2 among compliant subjects.

    16. Incidence tBPAR (Treated Biopsy-proven Acute Rejection) by Severity and Time to Event (Participants) [Month 12 and 24]

      Incidence tBPAR, defined as any condition where the subject received anti-rejection treatment and was histologically diagnosed as acute rejection (according to the Banff 2009 criteria), by severity (grade IA, IB, IIA, IIB, III) and time to event. Grades for T-cell mediated rejection, with increasing severity: Type IA - Significant interstitial infiltration (> 25% of parenchyma) and foci of moderate tubulitis (> 4 mononuclear cells/tubular cross section or group of 10 tubular cells). Type IB - Significant interstitial infiltration (> 25% of parenchyma) and foci of severe tubulitis (> 10 mononuclear cells/tubular cross section or group of 10 tubular cells). Type IIA - Mild to moderate intimal arteritis Type IIB - Severe intimal arteritis comprising > 25% of the lumenal area Type III - Transmural (full vessel wall thickness) arteritis and/or arterial fibrinoid change and necrosis of medial smooth muscle cells (with accompanying lymphocytic inflammation)

    17. Incidence tBPAR (Treated Biopsy-proven Acute Rejection) by Severity and Time to Event (Events) [Month 12 and 24]

      Incidence tBPAR, defined as any condition where the subject received anti-rejection treatment and was histologically diagnosed as acute rejection (according to the Banff 2009 criteria), by severity (grade IA, IB, IIA, IIB, III) and time to event. Grades for T-cell mediated rejection, with increasing severity: Type IA - Significant interstitial infiltration (> 25% of parenchyma) and foci of moderate tubulitis (> 4 mononuclear cells/tubular cross section or group of 10 tubular cells). Type IB - Significant interstitial infiltration (> 25% of parenchyma) and foci of severe tubulitis (> 10 mononuclear cells/tubular cross section or group of 10 tubular cells). Type IIA - Mild to moderate intimal arteritis Type IIB - Severe intimal arteritis comprising > 25% of the lumenal area Type III - Transmural (full vessel wall thickness) arteritis and/or arterial fibrinoid change and necrosis of medial smooth muscle cells (with accompanying lymphocytic inflammation)

    18. Incidence of tBPAR (Treated Biopsy-proven Acute Rejection) Excluding Grade IA Rejections [Month 12 and 24]

      Incidence of tBPAR, defined as any condition where the subject received anti-rejection treatment and was histologically diagnosed as acute rejection (according to the Banff 2009 criteria), excluding grade IA rejections. Grades for T-cell mediated rejection, with increasing severity: Type IA - Significant interstitial infiltration (> 25% of parenchyma) and foci of moderate tubulitis (> 4 mononuclear cells/tubular cross section or group of 10 tubular cells). Type IB - Significant interstitial infiltration (> 25% of parenchyma) and foci of severe tubulitis (> 10 mononuclear cells/tubular cross section or group of 10 tubular cells). Type IIA - Mild to moderate intimal arteritis Type IIB - Severe intimal arteritis comprising > 25% of the lumenal area Type III - Transmural (full vessel wall thickness) arteritis and/or arterial fibrinoid change and necrosis of medial smooth muscle cells (with accompanying lymphocytic inflammation)

    19. Incidence of Composite of tBPAR (Treated Biopsy-proven Acute Rejection)or eGRF<50 mL/Min/1.73m2 by Subgroup [Month 12 and 24]

      Incidence of composite of tBPAR or eGRF<50 mL/min/1.73m2 by subgroup

    20. Incidence of tBPAR (Excluding Grade IA Rejections) or GFR<50 mL/Min/1.73m2 [Month 12 and 24]

      Incidence of tBPAR (excluding grade IA rejections) or GFR<50 mL/min/1.73m2

    21. Incidence of Failure on the Composite of (Treated Biopsy Proven Acute Rejection (tBPAR), Graft Loss or Death or Loss to Follow-up [Month 12 and 24]

      Incidence of failure on the composite of (treated biopsy proven acute rejection (tBPAR), graft loss or death or loss to follow-up

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    1. Written informed consent obtained.

    2. Subject randomized within 24 hr of completion of transplant surgery.

    3. Recipient of a kidney with a cold ischemia time < 30 hours.

    4. Recipient of a primary (or secondary, if first graft is not lost due to immunological reasons) renal transplant from a deceased heart beating, living unrelated, living related non-human leukocyte antigen identical or an expanded criteria donor.

    Exclusion Criteria:

    1. Subject unable to tolerate oral medication at time of randomization.

    2. Use of other investigational drugs at the time of enrollment.

    3. History of hypersensitivity to any of the study drugs or to drugs of similar chemical classes.

    4. Multi-organ transplant recipient.

    5. Recipient of ABO incompatible allograft or complement-dependent lymphocytotoxic (CDC) crossmatch positive transplant.

    6. Subject at high immunological risk for rejection as determined by local practice for assessment of anti-donor reactivity e.g. high PRA, presence of pre-existing DSA.

    7. Subject who is HIV-positive.

    8. HBsAg and/or a HCV positive subject with evidence of elevated LFTs (ALT/AST levels ≥ 2.5 times ULN). Viral serology results obtained within 6 months prior to randomization are acceptable.

    9. Recipient of a kidney from a donor who tests positive for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg) or anti-hepatitis C virus (HCV).

    10. Subject with a BMI greater than 35.

    11. Subject with severe systemic infections, current or within the two weeks prior to randomization.

    12. Subject requiring systemic anticoagulation.

    13. History of malignancy of any organ system.

    14. Subject with severe restrictive or obstructive pulmonary disorders.

    15. Subject with severe hypercholesterolemia or hypertriglyceridemia that cannot be controlled.

    16. Subject with white blood cell (WBC) count ≤ 2,000 /mm3 or with platelet count ≤ 50,000 /mm3.

    17. Pregnant or nursing (lactating) women.

    18. Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using effective methods of contraception during dosing of study treatment.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Novartis Investigative Site Birmingham Alabama United States 35233
    2 Novartis Investigative Site Loma Linda California United States 92354
    3 Novartis Investigative Site Los Angeles California United States 90033
    4 Novartis Investigative Site Los Angeles California United States 90048
    5 Novartis Investigative Site Sacramento California United States 95817-1460
    6 Novartis Investigative Site San Diego California United States 92123
    7 Novartis Investigative Site San Francisco California United States 94115
    8 Novartis Investigative Site San Francisco California United States 94143-0116
    9 Novartis Investigative Site Aurora Colorado United States 80045
    10 Novartis Investigative Site Denver Colorado United States 80210
    11 Novartis Investigative Site Chicago Illinois United States 60612
    12 Novartis Investigative Site Baltimore Maryland United States 21201
    13 Novartis Investigative Site Boston Massachusetts United States 02114
    14 Novartis Investigative Site Boston Massachusetts United States 02215
    15 Novartis Investigative Site Burlington Massachusetts United States 01805
    16 Novartis Investigative Site Ann Arbor Michigan United States 48109-0331
    17 Novartis Investigative Site Detroit Michigan United States 48202
    18 Novartis Investigative Site Saint Louis Missouri United States 63110
    19 Novartis Investigative Site Livingston New Jersey United States 07039
    20 Novartis Investigative Site Bronx New York United States 10467
    21 Novartis Investigative Site Buffalo New York United States 14215
    22 Novartis Investigative Site Chapel Hill North Carolina United States 27599
    23 Novartis Investigative Site Durham North Carolina United States 27710
    24 Novartis Investigative Site Winston-Salem North Carolina United States 27157
    25 Novartis Investigative Site Cleveland Ohio United States 44106-5048
    26 Novartis Investigative Site Cleveland Ohio United States 44195
    27 Novartis Investigative Site Columbus Ohio United States 43210
    28 Novartis Investigative Site Harrisburg Pennsylvania United States 17105-8700
    29 Novartis Investigative Site Providence Rhode Island United States 02903
    30 Novartis Investigative Site Charleston South Carolina United States 29425
    31 Novartis Investigative Site Nashville Tennessee United States 37212-3139
    32 Novartis Investigative Site Dallas Texas United States 75246
    33 Novartis Investigative Site Fort Worth Texas United States 76104
    34 Novartis Investigative Site Houston Texas United States 77030-2400
    35 Novartis Investigative Site Houston Texas United States 77030
    36 Novartis Investigative Site Salt Lake City Utah United States 84132
    37 Novartis Investigative Site Charlottesville Virginia United States 22908
    38 Novartis Investigative Site Seattle Washington United States 98195
    39 Novartis Investigative Site Madison Wisconsin United States 53705
    40 Novartis Investigative Site Milwaukee Wisconsin United States 53226
    41 Novartis Investigative Site Caba Buenos Aires Argentina C1181ACH
    42 Novartis Investigative Site San Martin Buenos Aires Argentina C1107BEA
    43 Novartis Investigative Site Buenos Aires Argentina W3400ABH
    44 Novartis Investigative Site Cordoba Argentina X5016KEH
    45 Novartis Investigative Site Cordoba Argentina X5016KET
    46 Novartis Investigative Site Corrientes Argentina W3400
    47 Novartis Investigative Site Santa Fe Argentina S3000EPV
    48 Novartis Investigative Site Camperdown New South Wales Australia 2050
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    51 Novartis Investigative Site Woolloongabba Queensland Australia 4102
    52 Novartis Investigative Site Adelaide South Australia Australia 5000
    53 Novartis Investigative Site Clayton Victoria Australia 3168
    54 Novartis Investigative Site Heidelberg Victoria Australia 3084
    55 Novartis Investigative Site Parkville Victoria Australia 3050
    56 Novartis Investigative Site Murdoch Western Australia Australia 6150
    57 Novartis Investigative Site Nedlands Western Australia Australia 6009
    58 Novartis Investigative Site Innsbruck Tyrol Austria 6020
    59 Novartis Investigative Site Linz Austria A-4010
    60 Novartis Investigative Site Edegem Antwerpen Belgium 2650
    61 Novartis Investigative Site Bruxelles Belgium 1070
    62 Novartis Investigative Site Leuven Belgium 3000
    63 Novartis Investigative Site Liege Belgium 4000
    64 Novartis Investigative Site Porto Alegre RS Brazil 90020-090
    65 Novartis Investigative Site Sao Paulo SP Brazil 05403 000
    66 Novartis Investigative Site São Paulo SP Brazil 04038-002
    67 Novartis Investigative Site Sofia BGR Bulgaria 1431
    68 Novartis Investigative Site Santiago Chile 8207257
    69 Novartis Investigative Site Cali Valle Del Cauca Colombia
    70 Novartis Investigative Site Bogota Colombia
    71 Novartis Investigative Site Rijeka Croatia 51000
    72 Novartis Investigative Site Zagreb Croatia 10000
    73 Novartis Investigative Site Zagreb Croatia 1000
    74 Novartis Investigative Site Brno Czechia 656 91
    75 Novartis Investigative Site Praha 4 Czechia 140 00
    76 Novartis Investigative Site Mansoura Egypt
    77 Novartis Investigative Site Nice Cedex1 France 06001
    78 Novartis Investigative Site Tours Cedex 9 Indre Et Loire France 37044
    79 Novartis Investigative Site Montpellier Cedex 5 France 34295
    80 Novartis Investigative Site Paris cedex 15 France 75015
    81 Novartis Investigative Site Reims France 51092
    82 Novartis Investigative Site Regensburg Bavaria Germany 93053
    83 Novartis Investigative Site Berlin Germany 12203
    84 Novartis Investigative Site Berlin Germany 13353
    85 Novartis Investigative Site Essen Germany 45147
    86 Novartis Investigative Site Hannover Muenden Germany 34346
    87 Novartis Investigative Site Hannover Germany 30625
    88 Novartis Investigative Site Heidelberg Germany 69120
    89 Novartis Investigative Site Kaiserslautern Germany 67655
    90 Novartis Investigative Site Koeln Germany 51109
    91 Novartis Investigative Site Leipzig Germany 04103
    92 Novartis Investigative Site Muenchen Germany 81675
    93 Novartis Investigative Site München Germany 81377
    94 Novartis Investigative Site Thessaloniki GR Greece 546 42
    95 Novartis Investigative Site Athens Greece 106 76
    96 Novartis Investigative Site Athens Greece 11527
    97 Novartis Investigative Site Patras Greece 265 00
    98 Novartis Investigative Site New Delhi Delhi India 110 017
    99 Novartis Investigative Site Bangalore Karnataka India 560 055
    100 Novartis Investigative Site Mumbai Maharashtra India 400 016
    101 Novartis Investigative Site Vellore Tamil Nadu India 632004
    102 Novartis Investigative Site Petach Tikva Israel 49100
    103 Novartis Investigative Site Tel Aviv Israel 64239
    104 Novartis Investigative Site Bari BA Italy 70124
    105 Novartis Investigative Site Bologna BO Italy 40138
    106 Novartis Investigative Site Milano MI Italy 20162
    107 Novartis Investigative Site Padova PD Italy 35128
    108 Novartis Investigative Site Parma PR Italy 43100
    109 Novartis Investigative Site Roma RM Italy 00144
    110 Novartis Investigative Site Roma RM Italy 00168
    111 Novartis Investigative Site Siena SI Italy 53100
    112 Novartis Investigative Site Torino TO Italy 10126
    113 Novartis Investigative Site Novara Italy 28100
    114 Novartis Investigative Site Nagoya-city Aichi Japan 466-8650
    115 Novartis Investigative Site Toyoake city Aichi Japan 470 1192
    116 Novartis Investigative Site Chiba-city Chiba Japan 260-8712
    117 Novartis Investigative Site Seoul Korea Korea, Republic of 05505
    118 Novartis Investigative Site Seoul Korea Korea, Republic of 06351
    119 Novartis Investigative Site Seoul Korea, Republic of 03722
    120 Novartis Investigative Site Kuwait Kuwait
    121 Novartis Investigative Site Ashrafieh Lebanon 166830
    122 Novartis Investigative Site Saida Lebanon 652
    123 Novartis Investigative Site Saida Lebanon
    124 Novartis Investigative Site Kuala Lumpur Malaysia 50589
    125 Novartis Investigative Site Selangor Darul Ehsan Malaysia 68100
    126 Novartis Investigative Site Guadalajara Jalisco Mexico 44610
    127 Novartis Investigative Site Maastricht AZ Netherlands 5800
    128 Novartis Investigative Site Utrecht The Netherlands Netherlands 3508 GA
    129 Novartis Investigative Site Amsterdam Netherlands 1105 AZ
    130 Novartis Investigative Site Groningen Netherlands
    131 Novartis Investigative Site Leiden Netherlands 2333 ZA
    132 Novartis Investigative Site Nijmegen Netherlands
    133 Novartis Investigative Site Oslo Norway 0424
    134 Novartis Investigative Site Quezon City Philippines 1101
    135 Novartis Investigative Site Szczecin Pomorskie Poland 70-111
    136 Novartis Investigative Site Gdansk Poland 80 952
    137 Novartis Investigative Site Poznan Poland 60-355
    138 Novartis Investigative Site Poznan Poland 60-479
    139 Novartis Investigative Site Carnaxide Lisboa Portugal 2790-134
    140 Novartis Investigative Site Coimbra Portugal 3000 075
    141 Novartis Investigative Site Lisboa Portugal 1600190
    142 Novartis Investigative Site Lisbon Portugal 1069-166
    143 Novartis Investigative Site Porto Portugal 4200 319
    144 Novartis Investigative Site Ekaterinburg Russian Federation 620109
    145 Novartis Investigative Site Krasnodar Russian Federation 350086
    146 Novartis Investigative Site Moscow Russian Federation 123182
    147 Novartis Investigative Site Moscow Russian Federation 129010
    148 Novartis Investigative Site Nizhnii Novgorod Russian Federation 603000
    149 Novartis Investigative Site Volzhskiy Russian Federation 404120
    150 Novartis Investigative Site Dammam Saudi Arabia 15215
    151 Novartis Investigative Site Jeddah Saudi Arabia 21499
    152 Novartis Investigative Site Riyadh Saudi Arabia 11159
    153 Novartis Investigative Site Belgrade Serbia 11000
    154 Novartis Investigative Site Nis Serbia 18000
    155 Novartis Investigative Site Novi Sad Serbia
    156 Novartis Investigative Site Singapore Singapore 169608
    157 Novartis Investigative Site Banská Bystrica Slovakia 97517
    158 Novartis Investigative Site Bratislava Slovakia 833 05
    159 Novartis Investigative Site Kosice Slovakia 04166
    160 Novartis Investigative Site Martin Slovakia 03659
    161 Novartis Investigative Site Ljubljana Slovenia 1000
    162 Novartis Investigative Site Cape Town Western Province South Africa 7925
    163 Novartis Investigative Site Granada Andalucia Spain 18014
    164 Novartis Investigative Site Hospitalet de Llobregat Barcelona Spain 08907
    165 Novartis Investigative Site Santander Cantabria Spain 39008
    166 Novartis Investigative Site Barcelona Catalunya Spain 08003
    167 Novartis Investigative Site Barcelona Catalunya Spain 08036
    168 Novartis Investigative Site Valencia Comunidad Valenciana Spain 46017
    169 Novartis Investigative Site La Laguna Santa Cruz De Tenerife Spain 38320
    170 Novartis Investigative Site Madrid Spain 28034
    171 Novartis Investigative Site Madrid Spain 28041
    172 Novartis Investigative Site Zaragoza Spain 50009
    173 Novartis Investigative Site Göteborg Sweden SE-413 45
    174 Novartis Investigative Site Stockholm Sweden 14186
    175 Novartis Investigative Site Uppsala Sweden 751 85
    176 Novartis Investigative Site Bern Switzerland 3010
    177 Novartis Investigative Site Tainan Taiwan ROC Taiwan 70421
    178 Novartis Investigative Site Taichung Taiwan 40705
    179 Novartis Investigative Site Taipei Taiwan 10002
    180 Novartis Investigative Site Ratchathewi Bangkok Thailand 10400
    181 Novartis Investigative Site Bangkok Thailand 10400
    182 Novartis Investigative Site Antalya Turkey 07070
    183 Novartis Investigative Site Istanbul Turkey 34093
    184 Novartis Investigative Site Mecidiyekoy/Istanbul Turkey 34394

    Sponsors and Collaborators

    • Novartis Pharmaceuticals

    Investigators

    • Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

    Study Documents (Full-Text)

    More Information

    Publications

    None provided.
    Responsible Party:
    Novartis Pharmaceuticals
    ClinicalTrials.gov Identifier:
    NCT01950819
    Other Study ID Numbers:
    • CRAD001A2433
    • 2013-000322-66
    • NCT02316938
    First Posted:
    Sep 26, 2013
    Last Update Posted:
    Jan 30, 2019
    Last Verified:
    Jan 1, 2019
    Individual Participant Data (IPD) Sharing Statement:
    Undecided
    Plan to Share IPD:
    Undecided
    Keywords provided by Novartis Pharmaceuticals
    kidney failure
    dialysis
    renal failure
    transplantation
    Additional relevant MeSH terms:
    Kidney Diseases
    Renal Insufficiency, Chronic
    Kidney Failure, Chronic
    Cyclosporine
    Prednisone
    Methylprednisolone
    Tacrolimus
    Thymoglobulin
    Cyclosporins
    Basiliximab

    Study Results

    Participant Flow

    Recruitment Details The full analysis set consisted of all randomized and transplanted patients. The safet set consisted of all patients who received at least one dose of study drug
    Pre-assignment Detail 2226 patients screened; 2037 patients transplanted and randomized to treatment.
    Arm/Group Title EVR+rCNI MPA+sCNI
    Arm/Group Description Everolimus with reduced calcineurin inhibitor- everolimus (target trough level of 3-8 ng/mL) in combination with reduced exposure to CNI (cyclosporine or tacrolimus) Mycophenolate (mycophenolic acid sodium or mycophenolate mofetil) in combination with standard exposure to calcineurin inhibitor (cyclosporine or tacrolimus).
    Period Title: Overall Study
    STARTED 1022 1015
    COMPLETED 893 881
    NOT COMPLETED 129 134

    Baseline Characteristics

    Arm/Group Title EVR+rCNI MPA+sCNI Total
    Arm/Group Description Everolimus with reduced calcineurin inhibitor- everolimus (target trough level of 3-8 ng/mL) in combination with reduced exposure to CNI (cyclosporine or tacrolimus) Mycophenolate (mycophenolic acid sodium or mycophenolate mofetil) in combination with standard exposure to calcineurin inhibitor (cyclosporine or tacrolimus). Total of all reporting groups
    Overall Participants 1022 1015 2037
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    48.79
    (14.123)
    48.75
    (14.515)
    48.77
    (14.316)
    Sex: Female, Male (Count of Participants)
    Female
    312
    30.5%
    308
    30.3%
    620
    30.4%
    Male
    710
    69.5%
    707
    69.7%
    1417
    69.6%
    Race/Ethnicity, Customized (Count of Participants)
    Hispany or Latino
    157
    15.4%
    132
    13%
    289
    14.2%
    not Hispanic or Latino
    646
    63.2%
    661
    65.1%
    1307
    64.2%
    Unknown or not reported
    219
    21.4%
    222
    21.9%
    441
    21.6%
    Race/Ethnicity, Customized (Count of Participants)
    Caucasian
    743
    72.7%
    735
    72.4%
    1478
    72.6%
    Asian
    136
    13.3%
    157
    15.5%
    293
    14.4%
    Black
    43
    4.2%
    35
    3.4%
    78
    3.8%
    Other
    100
    9.8%
    88
    8.7%
    188
    9.2%

    Outcome Measures

    1. Primary Outcome
    Title Incidence of Failure on the Composite of Treated Biopsy-proven Acute Rejection (tBPAR) or Estimated Glomerular Filtration Rate (eGFR) < 50 mL/Min/1.73m2.
    Description Incidence of failure on the composite of treated biopsy-proven acute rejection (tBPAR) or estimated glomerular filtration rate (eGFR) < 50 mL/min/1.73m2.
    Time Frame Month 12 is Primary, Month 24 secondary

    Outcome Measure Data

    Analysis Population Description
    full analysis set
    Arm/Group Title EVR+rCNI MPA+sCNI
    Arm/Group Description Everolimus with reduced calcineurin inhibitor- everolimus (target trough level of 3-8 ng/mL) in combination with reduced exposure to CNI (cyclosporine or tacrolimus) Mycophenolate (mycophenolic acid sodium or mycophenolate mofetil) in combination with standard exposure to calcineurin inhibitor (cyclosporine or tacrolimus).
    Measure Participants 1022 1015
    month 12
    489
    47.8%
    456
    44.9%
    month 24
    489
    47.8%
    443
    43.6%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection EVR+rCNI, MPA+sCNI
    Comments calculated at month 12
    Type of Statistical Test Non-Inferiority
    Comments p vale for non inferiority margin is 10 %
    Statistical Test of Hypothesis p-Value 0.001
    Comments
    Method Logistic Regression Model
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 3.0
    Confidence Interval (2-Sided) 95%
    -1.4 to 7.3
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    2. Secondary Outcome
    Title Incidence of Failure on the Composite of (Treated Biopsy Proven Acute Rejection (tBPAR), Graft Loss or Death
    Description Incidence of failure on the composite of (treated biopsy proven acute rejection (tBPAR), graft loss or death
    Time Frame Month 12 and 24

    Outcome Measure Data

    Analysis Population Description
    full analysis set
    Arm/Group Title EVR+rCNI MPA+sCNI
    Arm/Group Description Everolimus with reduced calcineurin inhibitor- everolimus (target trough level of 3-8 ng/mL) in combination with reduced exposure to CNI (cyclosporine or tacrolimus) Mycophenolate (mycophenolic acid sodium or mycophenolate mofetil) in combination with standard exposure to calcineurin inhibitor (cyclosporine or tacrolimus).
    Measure Participants 1022 1015
    month 12
    146
    14.3%
    131
    12.9%
    month 24
    169
    16.5%
    147
    14.5%
    3. Secondary Outcome
    Title Incidence of Failure on the Composite Endpoint of tBPAR, Graft Loss, Death or eGFR < 50 mL/Min/1.73m2
    Description Incidence of failure on the composite endpoint of tBPAR, graft loss, death or eGFR < 50 mL/min/1.73m2
    Time Frame Month 12 and 24

    Outcome Measure Data

    Analysis Population Description
    full analysis set
    Arm/Group Title EVR+rCNI MPA+sCNI
    Arm/Group Description Everolimus with reduced calcineurin inhibitor- everolimus (target trough level of 3-8 ng/mL) in combination with reduced exposure to CNI (cyclosporine or tacrolimus) Mycophenolate (mycophenolic acid sodium or mycophenolate mofetil) in combination with standard exposure to calcineurin inhibitor (cyclosporine or tacrolimus).
    Measure Participants 1022 1015
    month 12
    497
    48.6%
    466
    45.9%
    month 24
    497
    48.6%
    457
    45%
    4. Secondary Outcome
    Title Incidence of Failure on the Composite Endpoint of Graft Loss or Death.
    Description Incidence of failure on the composite endpoint of graft loss or death.
    Time Frame Month 12 and 24

    Outcome Measure Data

    Analysis Population Description
    full analysis set
    Arm/Group Title EVR+rCNI MPA+sCNI
    Arm/Group Description Everolimus with reduced calcineurin inhibitor- everolimus (target trough level of 3-8 ng/mL) in combination with reduced exposure to CNI (cyclosporine or tacrolimus) Mycophenolate (mycophenolic acid sodium or mycophenolate mofetil) in combination with standard exposure to calcineurin inhibitor (cyclosporine or tacrolimus).
    Measure Participants 1022 1015
    month 12
    51
    5%
    54
    5.3%
    month 24
    67
    6.6%
    65
    6.4%
    5. Secondary Outcome
    Title Incidence of Death, Graft Loss, tBPAR, BPAR, tAR, AR and Humoral Rejection
    Description Incidence of death, graft loss, tBPAR (treated biopsy proven acute rejection), BPAR (biopsy proven acute rejection), tAR (treated acute rejection), AR (acute rejection) and humoral rejection (aAMR : active antibody mediated rejection and cAMR: chronic antibody mediated rejection)
    Time Frame Month 12 and 24

    Outcome Measure Data

    Analysis Population Description
    full analysis set
    Arm/Group Title EVR+rCNI MPA+sCNI
    Arm/Group Description Everolimus with reduced calcineurin inhibitor- everolimus (target trough level of 3-8 ng/mL) in combination with reduced exposure to CNI (cyclosporine or tacrolimus) Mycophenolate (mycophenolic acid sodium or mycophenolate mofetil) in combination with standard exposure to calcineurin inhibitor (cyclosporine or tacrolimus).
    Measure Participants 1022 1015
    deaths month 12
    20
    2%
    28
    2.8%
    deaths month 24
    32
    3.1%
    36
    3.5%
    graft loss month 12
    33
    3.2%
    28
    2.8%
    graft loss month 24
    37
    3.6%
    32
    3.2%
    tBPAR month 12
    107
    10.5%
    91
    9%
    tBPAR month 24
    118
    11.5%
    98
    9.7%
    BPAR month 12
    114
    11.2%
    95
    9.4%
    BPAR month 24
    127
    12.4%
    104
    10.2%
    tAR month 12
    129
    12.6%
    117
    11.5%
    tAR month 24
    145
    14.2%
    126
    12.4%
    AR month 12
    147
    14.4%
    133
    13.1%
    AR month 24
    167
    16.3%
    144
    14.2%
    aAMR month 12
    73
    7.1%
    61
    6%
    aAMR month 24
    84
    8.2%
    69
    6.8%
    cAMR month 12
    9
    0.9%
    14
    1.4%
    cAMR month 24
    13
    1.3%
    18
    1.8%
    6. Secondary Outcome
    Title Incidence of eGFR < 50 mL/Min/1.73m2
    Description Incidence of eGFR < 50 mL/min/1.73m2
    Time Frame Month 12 and 24

    Outcome Measure Data

    Analysis Population Description
    full analysis set
    Arm/Group Title EVR+rCNI MPA+sCNI
    Arm/Group Description Everolimus with reduced calcineurin inhibitor- everolimus (target trough level of 3-8 ng/mL) in combination with reduced exposure to CNI (cyclosporine or tacrolimus) Mycophenolate (mycophenolic acid sodium or mycophenolate mofetil) in combination with standard exposure to calcineurin inhibitor (cyclosporine or tacrolimus).
    Measure Participants 1022 1015
    month 12
    456
    44.6%
    424
    41.8%
    month 24
    474
    46.4%
    423
    41.7%
    7. Secondary Outcome
    Title Renal Allograft Function : Mean Estimated Glomerular Filtration Rate, eGFR
    Description Renal allograft function : mean estimated glomerular filtration rate, eGFR
    Time Frame Baseline (week 4), Month 12 and 24

    Outcome Measure Data

    Analysis Population Description
    full analysis set
    Arm/Group Title EVR+rCNI MPA+sCNI
    Arm/Group Description Everolimus with reduced calcineurin inhibitor- everolimus (target trough level of 3-8 ng/mL) in combination with reduced exposure to CNI (cyclosporine or tacrolimus) Mycophenolate (mycophenolic acid sodium or mycophenolate mofetil) in combination with standard exposure to calcineurin inhibitor (cyclosporine or tacrolimus).
    Measure Participants 1022 1015
    baseline (week 4)
    53.13
    (0.765)
    52.25
    (0.684)
    month 12
    53.29
    (0.698)
    54.49
    (0.667)
    month 24
    52.63
    (0.744)
    54.91
    (0.719)
    8. Secondary Outcome
    Title Evolution of Renal Function, as eGFR, Over Time by Slope Analysis.
    Description Rate of change of renal function, as eGFR, calculated using MDRD4 formula (Coresh, 2003) and adjusted by covariates.
    Time Frame Month 12 and 24

    Outcome Measure Data

    Analysis Population Description
    full analysis set
    Arm/Group Title EVR+rCNI MPA+sCNI
    Arm/Group Description Everolimus with reduced calcineurin inhibitor- everolimus (target trough level of 3-8 ng/mL) in combination with reduced exposure to CNI (cyclosporine or tacrolimus) Mycophenolate (mycophenolic acid sodium or mycophenolate mofetil) in combination with standard exposure to calcineurin inhibitor (cyclosporine or tacrolimus).
    Measure Participants 1022 1015
    Mean (Standard Error) [mL / min / 1.73m2 / day]
    0.0001
    (0.0008)
    0.0047
    (0.0008)
    9. Secondary Outcome
    Title Renal Function Assessed by Creatinine Lab Values
    Description Mean Renal function as assessed in clinical practice, by ceatinine values. Analysis is done without considering missing values for analysis.
    Time Frame Month 12 and 24

    Outcome Measure Data

    Analysis Population Description
    full analysis set with measure
    Arm/Group Title EVR+rCNI MPA+sCNI
    Arm/Group Description Everolimus with reduced calcineurin inhibitor- everolimus (target trough level of 3-8 ng/mL) in combination with reduced exposure to CNI (cyclosporine or tacrolimus) Mycophenolate (mycophenolic acid sodium or mycophenolate mofetil) in combination with standard exposure to calcineurin inhibitor (cyclosporine or tacrolimus).
    Measure Participants 1022 1015
    screening baseline (creatinine, micromol/L)
    590.1
    (262.78)
    601.8
    (265.08)
    month 12 (creatinine, micromol/L)
    129.8
    (49.12)
    128.6
    (50.80)
    month 24 (creatinine, micromol/L)
    130.1
    (53.54)
    127.6
    (52.50)
    10. Secondary Outcome
    Title Renal Function by Alternative Formulae (e.g. CKD-EPI). eGFR Values Reported
    Description Mean Renal function as used in clinical practice, using different formula for calculation of renal function than MDRD4 (our primary efficacy parameter), and other alternate formulae (e.g. CKD-EPI). Analysis is done without considering missing values for analysis.
    Time Frame Month 12 and 24

    Outcome Measure Data

    Analysis Population Description
    full analysis set with measure
    Arm/Group Title EVR+rCNI MPA+sCNI
    Arm/Group Description Everolimus with reduced calcineurin inhibitor- everolimus (target trough level of 3-8 ng/mL) in combination with reduced exposure to CNI (cyclosporine or tacrolimus) Mycophenolate (mycophenolic acid sodium or mycophenolate mofetil) in combination with standard exposure to calcineurin inhibitor (cyclosporine or tacrolimus).
    Measure Participants 1022 1015
    eGFR (Hoek) baseline (mL/min/1.73m2)
    21.38
    (14.296)
    20.10
    (12.408)
    eGFR (Hoek) month 12 (mL/min/1.73m2)
    50.08
    (14.430)
    52.00
    (14.533)
    eGFR (Hoek) month 24 (mL/min/1.73m2)
    49.86
    (14.604)
    52.75
    (15.406)
    eGFR (MDRD4) baseline (mL/min/1.73m2)
    11.79
    (8.697)
    11.56
    (8.853)
    eGFR (MDRD4) month 12 (mL/min/1.73m2)
    57.59
    (19.685)
    57.58
    (18.768)
    eGFR (MDRD4) month 24 (mL/min/1.73m2)
    58.07
    (20.168)
    58.68
    (19.541)
    eGFR-CKDEPI baseline (mL/min/1.73m2)
    11.29
    (9.094)
    11.05
    (9.195)
    eGFR-CKDEPI month 12(mL/min/1.73m2)
    58.83
    (20.686)
    58.75
    (19.757)
    eGFR-CKDEPI month 24 (mL/min/1.73m2)
    59.39
    (21.077)
    59.95
    (20.652)
    11. Secondary Outcome
    Title Incidence of Adverse Events, Serious Adverse Events and Adverse Events Leading to Study Regimen Discontinuation.
    Description Incidence of adverse events, serious adverse events and adverse events leading to study regimen discontinuation.
    Time Frame Month 24

    Outcome Measure Data

    Analysis Population Description
    safety set 24 months analysis
    Arm/Group Title EVR+rCNI MPA+sCNI
    Arm/Group Description Everolimus with reduced calcineurin inhibitor- everolimus (target trough level of 3-8 ng/mL) in combination with reduced exposure to CNI (cyclosporine or tacrolimus) Mycophenolate (mycophenolic acid sodium or mycophenolate mofetil) in combination with standard exposure to calcineurin inhibitor (cyclosporine or tacrolimus).
    Measure Participants 1014 1012
    Count of Participants [Participants]
    276
    27%
    152
    15%
    12. Secondary Outcome
    Title Incidence of Cytomegalovirus and BK Virus, New Onset Diabetes Mellitus, Chronic Kidney Disease With Associated Proteinuria and Calcineurin Inhibitor Associated Adverse Events.
    Description Incidence of cytomegalovirus and BK virus, new onset diabetes mellitus, chronic kidney disease with associated proteinuria and calcineurin inhibitor associated adverse events.
    Time Frame Month 24

    Outcome Measure Data

    Analysis Population Description
    safety set
    Arm/Group Title EVR+rCNI MPA+sCNI
    Arm/Group Description Everolimus with reduced calcineurin inhibitor- everolimus (target trough level of 3-8 ng/mL) in combination with reduced exposure to CNI (cyclosporine or tacrolimus) Mycophenolate (mycophenolic acid sodium or mycophenolate mofetil) in combination with standard exposure to calcineurin inhibitor (cyclosporine or tacrolimus).
    Measure Participants 1014 1012
    clinical signs of CMV infection
    53
    5.2%
    132
    13%
    any BKV infection
    103
    10.1%
    154
    15.2%
    new onset of diabetes mellitus
    144
    14.1%
    138
    13.6%
    at least one event of interest
    871
    85.2%
    764
    75.3%
    13. Secondary Outcome
    Title Urinary Protein and Albumin Excretion by Treatment Estimated by Urinary Protein/Creatinine and Urinary Albumin/Creatinine Ratios.
    Description Mean urinary protein and albumin excretion by treatment estimated by mean urinary protein/creatinine and urinary albumin/creatinine ratios.
    Time Frame Baseline, Month 12 and 24

    Outcome Measure Data

    Analysis Population Description
    safety set with measure
    Arm/Group Title EVR+rCNI MPA+sCNI
    Arm/Group Description Everolimus with reduced calcineurin inhibitor- everolimus (target trough level of 3-8 ng/mL) in combination with reduced exposure to CNI (cyclosporine or tacrolimus) Mycophenolate (mycophenolic acid sodium or mycophenolate mofetil) in combination with standard exposure to calcineurin inhibitor (cyclosporine or tacrolimus).
    Measure Participants 1014 1012
    albumine /creatinine ratio baseline
    1019.75
    (2737.96)
    646.111
    (799.234)
    albumine /creatinine ratio month 12
    150.061
    (482.394)
    111.322
    (444.631)
    albumine /creatinine ratio month 24
    149.049
    (464.470)
    116.618
    (433.392)
    protein /creatinine ratio baseline
    1648.10
    (3768.22)
    1142.59
    (1003.69)
    protein /creatinine ratio month 12
    298.557
    (642.103)
    234.698
    (583.632)
    protein /creatinine ratio month 24
    290.242
    (588.119)
    233.009
    (524.383)
    14. Secondary Outcome
    Title Incidence of Major Cardiovascular Events.
    Description Incidence of major cardiovascular events by Preferred Term
    Time Frame Month 24

    Outcome Measure Data

    Analysis Population Description
    safety set
    Arm/Group Title EVR+rCNI MPA+sCNI
    Arm/Group Description Everolimus with reduced calcineurin inhibitor- everolimus (target trough level of 3-8 ng/mL) in combination with reduced exposure to CNI (cyclosporine or tacrolimus) Mycophenolate (mycophenolic acid sodium or mycophenolate mofetil) in combination with standard exposure to calcineurin inhibitor (cyclosporine or tacrolimus).
    Measure Participants 1014 1012
    Count of Participants [Participants]
    66
    6.5%
    86
    8.5%
    15. Secondary Outcome
    Title Incidence of Malignancies.
    Description Incidence of malignancies.
    Time Frame Month 24

    Outcome Measure Data

    Analysis Population Description
    safety set
    Arm/Group Title EVR+rCNI MPA+sCNI
    Arm/Group Description Everolimus with reduced calcineurin inhibitor- everolimus (target trough level of 3-8 ng/mL) in combination with reduced exposure to CNI (cyclosporine or tacrolimus) Mycophenolate (mycophenolic acid sodium or mycophenolate mofetil) in combination with standard exposure to calcineurin inhibitor (cyclosporine or tacrolimus).
    Measure Participants 1014 1012
    Count of Participants [Participants]
    41
    4%
    39
    3.8%
    16. Secondary Outcome
    Title Incidence of Failure on the Composite of Treated Biopsy-proven Acute Rejection (tBPAR) or Estimated Glomerular Filtration Rate (eGFR) < 50 mL/Min/1.73m2 Among Compliant Subjects.
    Description Incidence of failure on the composite of treated biopsy-proven acute rejection (tBPAR) or estimated glomerular filtration rate (eGFR) < 50 mL/min/1.73m2 among compliant subjects.
    Time Frame Month 12 and 24

    Outcome Measure Data

    Analysis Population Description
    compliance set
    Arm/Group Title EVR+rCNI MPA+sCNI
    Arm/Group Description Everolimus with reduced calcineurin inhibitor- everolimus (target trough level of 3-8 ng/mL) in combination with reduced exposure to CNI (cyclosporine or tacrolimus) Mycophenolate (mycophenolic acid sodium or mycophenolate mofetil) in combination with standard exposure to calcineurin inhibitor (cyclosporine or tacrolimus).
    Measure Participants 187 277
    month 12
    60
    5.9%
    106
    10.4%
    month 24
    62
    6.1%
    102
    10%
    17. Secondary Outcome
    Title Incidence tBPAR (Treated Biopsy-proven Acute Rejection) by Severity and Time to Event (Participants)
    Description Incidence tBPAR, defined as any condition where the subject received anti-rejection treatment and was histologically diagnosed as acute rejection (according to the Banff 2009 criteria), by severity (grade IA, IB, IIA, IIB, III) and time to event. Grades for T-cell mediated rejection, with increasing severity: Type IA - Significant interstitial infiltration (> 25% of parenchyma) and foci of moderate tubulitis (> 4 mononuclear cells/tubular cross section or group of 10 tubular cells). Type IB - Significant interstitial infiltration (> 25% of parenchyma) and foci of severe tubulitis (> 10 mononuclear cells/tubular cross section or group of 10 tubular cells). Type IIA - Mild to moderate intimal arteritis Type IIB - Severe intimal arteritis comprising > 25% of the lumenal area Type III - Transmural (full vessel wall thickness) arteritis and/or arterial fibrinoid change and necrosis of medial smooth muscle cells (with accompanying lymphocytic inflammation)
    Time Frame Month 12 and 24

    Outcome Measure Data

    Analysis Population Description
    full analysis set
    Arm/Group Title EVR+rCNI MPA+sCNI
    Arm/Group Description Everolimus with reduced calcineurin inhibitor- everolimus (target trough level of 3-8 ng/mL) in combination with reduced exposure to CNI (cyclosporine or tacrolimus) Mycophenolate (mycophenolic acid sodium or mycophenolate mofetil) in combination with standard exposure to calcineurin inhibitor (cyclosporine or tacrolimus).
    Measure Participants 1022 1015
    Patient's maximum tBPAR grade : no grade (missing)
    25
    2.4%
    18
    1.8%
    Patient's maximum tBPAR grade : grade IA
    34
    3.3%
    36
    3.5%
    Patient's maximum tBPAR grade : grade IB
    23
    2.3%
    17
    1.7%
    Patient's maximum tBPAR grade : grade IIA
    21
    2.1%
    24
    2.4%
    Patient's maximum tBPAR grade : grade IIB
    9
    0.9%
    3
    0.3%
    Patient's maximum tBPAR grade : grade III
    6
    0.6%
    0
    0%
    18. Secondary Outcome
    Title Incidence tBPAR (Treated Biopsy-proven Acute Rejection) by Severity and Time to Event (Events)
    Description Incidence tBPAR, defined as any condition where the subject received anti-rejection treatment and was histologically diagnosed as acute rejection (according to the Banff 2009 criteria), by severity (grade IA, IB, IIA, IIB, III) and time to event. Grades for T-cell mediated rejection, with increasing severity: Type IA - Significant interstitial infiltration (> 25% of parenchyma) and foci of moderate tubulitis (> 4 mononuclear cells/tubular cross section or group of 10 tubular cells). Type IB - Significant interstitial infiltration (> 25% of parenchyma) and foci of severe tubulitis (> 10 mononuclear cells/tubular cross section or group of 10 tubular cells). Type IIA - Mild to moderate intimal arteritis Type IIB - Severe intimal arteritis comprising > 25% of the lumenal area Type III - Transmural (full vessel wall thickness) arteritis and/or arterial fibrinoid change and necrosis of medial smooth muscle cells (with accompanying lymphocytic inflammation)
    Time Frame Month 12 and 24

    Outcome Measure Data

    Analysis Population Description
    full analysis set
    Arm/Group Title EVR+rCNI MPA+sCNI
    Arm/Group Description Everolimus with reduced calcineurin inhibitor- everolimus (target trough level of 3-8 ng/mL) in combination with reduced exposure to CNI (cyclosporine or tacrolimus) Mycophenolate (mycophenolic acid sodium or mycophenolate mofetil) in combination with standard exposure to calcineurin inhibitor (cyclosporine or tacrolimus).
    Measure Participants 1022 1015
    overall number of tBPAR regardless of grade
    146
    116
    number of tBPAR regardless of grade days 1-90
    72
    63
    number of tBPAR regardless of grade days 91-180
    24
    14
    number of tBPAR regardless of grade days 181-360
    25
    20
    number of tBPAR regardless of grade days 361-540
    12
    15
    number of tBPAR regardless of grade days 541-720
    11
    2
    number of tBPAR regardless of grade days 721-810
    2
    2
    19. Secondary Outcome
    Title Incidence of tBPAR (Treated Biopsy-proven Acute Rejection) Excluding Grade IA Rejections
    Description Incidence of tBPAR, defined as any condition where the subject received anti-rejection treatment and was histologically diagnosed as acute rejection (according to the Banff 2009 criteria), excluding grade IA rejections. Grades for T-cell mediated rejection, with increasing severity: Type IA - Significant interstitial infiltration (> 25% of parenchyma) and foci of moderate tubulitis (> 4 mononuclear cells/tubular cross section or group of 10 tubular cells). Type IB - Significant interstitial infiltration (> 25% of parenchyma) and foci of severe tubulitis (> 10 mononuclear cells/tubular cross section or group of 10 tubular cells). Type IIA - Mild to moderate intimal arteritis Type IIB - Severe intimal arteritis comprising > 25% of the lumenal area Type III - Transmural (full vessel wall thickness) arteritis and/or arterial fibrinoid change and necrosis of medial smooth muscle cells (with accompanying lymphocytic inflammation)
    Time Frame Month 12 and 24

    Outcome Measure Data

    Analysis Population Description
    full analysis set
    Arm/Group Title EVR+rCNI MPA+sCNI
    Arm/Group Description Everolimus with reduced calcineurin inhibitor- everolimus (target trough level of 3-8 ng/mL) in combination with reduced exposure to CNI (cyclosporine or tacrolimus) Mycophenolate (mycophenolic acid sodium or mycophenolate mofetil) in combination with standard exposure to calcineurin inhibitor (cyclosporine or tacrolimus).
    Measure Participants 1022 1015
    month 12
    66
    6.5%
    53
    5.2%
    month 24
    74
    7.2%
    55
    5.4%
    20. Secondary Outcome
    Title Incidence of Composite of tBPAR (Treated Biopsy-proven Acute Rejection)or eGRF<50 mL/Min/1.73m2 by Subgroup
    Description Incidence of composite of tBPAR or eGRF<50 mL/min/1.73m2 by subgroup
    Time Frame Month 12 and 24

    Outcome Measure Data

    Analysis Population Description
    full analysis set
    Arm/Group Title EVR+rCNI MPA+sCNI
    Arm/Group Description Everolimus with reduced calcineurin inhibitor- everolimus (target trough level of 3-8 ng/mL) in combination with reduced exposure to CNI (cyclosporine or tacrolimus) Mycophenolate (mycophenolic acid sodium or mycophenolate mofetil) in combination with standard exposure to calcineurin inhibitor (cyclosporine or tacrolimus).
    Measure Participants 1022 1015
    month 12
    489
    47.8%
    456
    44.9%
    month 24
    489
    47.8%
    443
    43.6%
    21. Secondary Outcome
    Title Incidence of tBPAR (Excluding Grade IA Rejections) or GFR<50 mL/Min/1.73m2
    Description Incidence of tBPAR (excluding grade IA rejections) or GFR<50 mL/min/1.73m2
    Time Frame Month 12 and 24

    Outcome Measure Data

    Analysis Population Description
    full analysis set
    Arm/Group Title EVR+rCNI MPA+sCNI
    Arm/Group Description Everolimus with reduced calcineurin inhibitor- everolimus (target trough level of 3-8 ng/mL) in combination with reduced exposure to CNI (cyclosporine or tacrolimus) Mycophenolate (mycophenolic acid sodium or mycophenolate mofetil) in combination with standard exposure to calcineurin inhibitor (cyclosporine or tacrolimus).
    Measure Participants 1022 1015
    month 12
    475
    46.5%
    441
    43.4%
    month 24
    475
    46.5%
    426
    42%
    22. Secondary Outcome
    Title Incidence of Failure on the Composite of (Treated Biopsy Proven Acute Rejection (tBPAR), Graft Loss or Death or Loss to Follow-up
    Description Incidence of failure on the composite of (treated biopsy proven acute rejection (tBPAR), graft loss or death or loss to follow-up
    Time Frame Month 12 and 24

    Outcome Measure Data

    Analysis Population Description
    full analysis set
    Arm/Group Title EVR+rCNI MPA+sCNI
    Arm/Group Description Everolimus with reduced calcineurin inhibitor- everolimus (target trough level of 3-8 ng/mL) in combination with reduced exposure to CNI (cyclosporine or tacrolimus) Mycophenolate (mycophenolic acid sodium or mycophenolate mofetil) in combination with standard exposure to calcineurin inhibitor (cyclosporine or tacrolimus).
    Measure Participants 1022 1015
    month 12
    181
    17.7%
    170
    16.7%
    month 24
    218
    21.3%
    201
    19.8%

    Adverse Events

    Time Frame Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 4 years.
    Adverse Event Reporting Description treatment emergent AE / SAE . Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
    Arm/Group Title Everolimus Plus@Reduced CNI MPA Plus Standard@CNI
    Arm/Group Description Everolimus plus@reduced CNI MPA plus standard@CNI
    All Cause Mortality
    Everolimus Plus@Reduced CNI MPA Plus Standard@CNI
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 20/1014 (2%) 29/1012 (2.9%)
    Serious Adverse Events
    Everolimus Plus@Reduced CNI MPA Plus Standard@CNI
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 593/1014 (58.5%) 613/1012 (60.6%)
    Blood and lymphatic system disorders
    Agranulocytosis 2/1014 (0.2%) 0/1012 (0%)
    Anaemia 14/1014 (1.4%) 6/1012 (0.6%)
    Atypical haemolytic uraemic syndrome 1/1014 (0.1%) 0/1012 (0%)
    Bone marrow failure 0/1014 (0%) 1/1012 (0.1%)
    Febrile neutropenia 0/1014 (0%) 5/1012 (0.5%)
    Granulocytopenia 0/1014 (0%) 1/1012 (0.1%)
    Haemolysis 2/1014 (0.2%) 0/1012 (0%)
    Haemolytic uraemic syndrome 1/1014 (0.1%) 2/1012 (0.2%)
    Iron deficiency anaemia 0/1014 (0%) 1/1012 (0.1%)
    Leukocytosis 1/1014 (0.1%) 0/1012 (0%)
    Leukopenia 4/1014 (0.4%) 12/1012 (1.2%)
    Lymphadenopathy 1/1014 (0.1%) 0/1012 (0%)
    Lymphatic obstruction 1/1014 (0.1%) 0/1012 (0%)
    Lymphopenia 0/1014 (0%) 1/1012 (0.1%)
    Nephrogenic anaemia 0/1014 (0%) 1/1012 (0.1%)
    Neutropenia 1/1014 (0.1%) 6/1012 (0.6%)
    Pancytopenia 2/1014 (0.2%) 1/1012 (0.1%)
    Polycythaemia 0/1014 (0%) 2/1012 (0.2%)
    Sickle cell anaemia with crisis 1/1014 (0.1%) 0/1012 (0%)
    Splenomegaly 0/1014 (0%) 1/1012 (0.1%)
    Thrombocytopenia 3/1014 (0.3%) 1/1012 (0.1%)
    Thrombotic microangiopathy 8/1014 (0.8%) 3/1012 (0.3%)
    Cardiac disorders
    Acute coronary syndrome 4/1014 (0.4%) 2/1012 (0.2%)
    Acute myocardial infarction 6/1014 (0.6%) 6/1012 (0.6%)
    Angina pectoris 6/1014 (0.6%) 5/1012 (0.5%)
    Angina unstable 1/1014 (0.1%) 1/1012 (0.1%)
    Aortic valve stenosis 0/1014 (0%) 1/1012 (0.1%)
    Arrhythmia 0/1014 (0%) 1/1012 (0.1%)
    Arrhythmia supraventricular 1/1014 (0.1%) 0/1012 (0%)
    Arteriosclerosis coronary artery 0/1014 (0%) 2/1012 (0.2%)
    Atrial fibrillation 12/1014 (1.2%) 12/1012 (1.2%)
    Atrial flutter 4/1014 (0.4%) 1/1012 (0.1%)
    Bradycardia 3/1014 (0.3%) 1/1012 (0.1%)
    Cardiac arrest 4/1014 (0.4%) 4/1012 (0.4%)
    Cardiac asthma 0/1014 (0%) 1/1012 (0.1%)
    Cardiac dysfunction 1/1014 (0.1%) 0/1012 (0%)
    Cardiac failure 9/1014 (0.9%) 7/1012 (0.7%)
    Cardiac failure acute 2/1014 (0.2%) 0/1012 (0%)
    Cardiac failure chronic 2/1014 (0.2%) 1/1012 (0.1%)
    Cardiac failure congestive 6/1014 (0.6%) 3/1012 (0.3%)
    Cardio-respiratory arrest 1/1014 (0.1%) 0/1012 (0%)
    Cardiorenal syndrome 1/1014 (0.1%) 0/1012 (0%)
    Coronary artery disease 2/1014 (0.2%) 6/1012 (0.6%)
    Coronary artery insufficiency 0/1014 (0%) 1/1012 (0.1%)
    Coronary artery stenosis 2/1014 (0.2%) 1/1012 (0.1%)
    Hypertensive heart disease 1/1014 (0.1%) 0/1012 (0%)
    Ischaemic cardiomyopathy 0/1014 (0%) 1/1012 (0.1%)
    Left ventricular failure 1/1014 (0.1%) 0/1012 (0%)
    Left ventricular hypertrophy 0/1014 (0%) 1/1012 (0.1%)
    Myocardial infarction 5/1014 (0.5%) 6/1012 (0.6%)
    Myocardial ischaemia 0/1014 (0%) 1/1012 (0.1%)
    Pericarditis 1/1014 (0.1%) 0/1012 (0%)
    Pericarditis constrictive 0/1014 (0%) 1/1012 (0.1%)
    Pulseless electrical activity 0/1014 (0%) 1/1012 (0.1%)
    Tachycardia 0/1014 (0%) 2/1012 (0.2%)
    Ventricular extrasystoles 0/1014 (0%) 1/1012 (0.1%)
    Ventricular tachyarrhythmia 1/1014 (0.1%) 0/1012 (0%)
    Ventricular tachycardia 1/1014 (0.1%) 0/1012 (0%)
    Congenital, familial and genetic disorders
    Arteriovenous malformation 0/1014 (0%) 1/1012 (0.1%)
    Congenital cystic kidney disease 0/1014 (0%) 1/1012 (0.1%)
    Congenital megaureter 1/1014 (0.1%) 0/1012 (0%)
    Hydrocele 1/1014 (0.1%) 2/1012 (0.2%)
    Tracheo-oesophageal fistula 0/1014 (0%) 1/1012 (0.1%)
    Ear and labyrinth disorders
    Mastoid effusion 1/1014 (0.1%) 0/1012 (0%)
    Sudden hearing loss 1/1014 (0.1%) 0/1012 (0%)
    Tinnitus 0/1014 (0%) 1/1012 (0.1%)
    Vertigo 1/1014 (0.1%) 0/1012 (0%)
    Endocrine disorders
    Goitre 1/1014 (0.1%) 0/1012 (0%)
    Hyperparathyroidism 1/1014 (0.1%) 0/1012 (0%)
    Hyperparathyroidism tertiary 0/1014 (0%) 1/1012 (0.1%)
    Eye disorders
    Cataract 1/1014 (0.1%) 3/1012 (0.3%)
    Glaucoma 0/1014 (0%) 1/1012 (0.1%)
    Optic ischaemic neuropathy 0/1014 (0%) 1/1012 (0.1%)
    Retinal detachment 0/1014 (0%) 1/1012 (0.1%)
    Vision blurred 0/1014 (0%) 1/1012 (0.1%)
    Visual acuity reduced 0/1014 (0%) 1/1012 (0.1%)
    Gastrointestinal disorders
    Abdominal hernia 4/1014 (0.4%) 2/1012 (0.2%)
    Abdominal pain 9/1014 (0.9%) 14/1012 (1.4%)
    Abdominal pain lower 1/1014 (0.1%) 1/1012 (0.1%)
    Abdominal pain upper 4/1014 (0.4%) 3/1012 (0.3%)
    Abdominal wall haematoma 1/1014 (0.1%) 1/1012 (0.1%)
    Acute abdomen 1/1014 (0.1%) 0/1012 (0%)
    Anal polyp 1/1014 (0.1%) 0/1012 (0%)
    Anogenital dysplasia 0/1014 (0%) 1/1012 (0.1%)
    Barrett's oesophagus 1/1014 (0.1%) 0/1012 (0%)
    Chronic gastritis 1/1014 (0.1%) 0/1012 (0%)
    Colitis 1/1014 (0.1%) 1/1012 (0.1%)
    Colitis ischaemic 1/1014 (0.1%) 0/1012 (0%)
    Colitis ulcerative 0/1014 (0%) 1/1012 (0.1%)
    Constipation 1/1014 (0.1%) 3/1012 (0.3%)
    Crohn's disease 1/1014 (0.1%) 1/1012 (0.1%)
    Diabetic gastroparesis 0/1014 (0%) 1/1012 (0.1%)
    Diarrhoea 27/1014 (2.7%) 55/1012 (5.4%)
    Diverticulum 1/1014 (0.1%) 0/1012 (0%)
    Diverticulum intestinal 1/1014 (0.1%) 0/1012 (0%)
    Diverticulum intestinal haemorrhagic 0/1014 (0%) 2/1012 (0.2%)
    Duodenal perforation 0/1014 (0%) 1/1012 (0.1%)
    Duodenal ulcer 0/1014 (0%) 1/1012 (0.1%)
    Encapsulating peritoneal sclerosis 1/1014 (0.1%) 0/1012 (0%)
    Enteritis 1/1014 (0.1%) 0/1012 (0%)
    Enterocolitis 2/1014 (0.2%) 1/1012 (0.1%)
    Food poisoning 0/1014 (0%) 1/1012 (0.1%)
    Gastric haemorrhage 1/1014 (0.1%) 0/1012 (0%)
    Gastric ulcer 0/1014 (0%) 1/1012 (0.1%)
    Gastritis 1/1014 (0.1%) 0/1012 (0%)
    Gastritis erosive 0/1014 (0%) 1/1012 (0.1%)
    Gastritis haemorrhagic 0/1014 (0%) 1/1012 (0.1%)
    Gastrointestinal fistula 1/1014 (0.1%) 0/1012 (0%)
    Gastrointestinal haemorrhage 2/1014 (0.2%) 4/1012 (0.4%)
    Gastrooesophageal reflux disease 0/1014 (0%) 1/1012 (0.1%)
    Haematochezia 1/1014 (0.1%) 0/1012 (0%)
    Haemorrhoidal haemorrhage 1/1014 (0.1%) 0/1012 (0%)
    Haemorrhoids 0/1014 (0%) 1/1012 (0.1%)
    Hernial eventration 1/1014 (0.1%) 0/1012 (0%)
    Hiatus hernia 0/1014 (0%) 1/1012 (0.1%)
    Ileus 5/1014 (0.5%) 2/1012 (0.2%)
    Impaired gastric emptying 1/1014 (0.1%) 1/1012 (0.1%)
    Inguinal hernia 2/1014 (0.2%) 5/1012 (0.5%)
    Intestinal obstruction 2/1014 (0.2%) 2/1012 (0.2%)
    Intestinal perforation 2/1014 (0.2%) 1/1012 (0.1%)
    Intra-abdominal fluid collection 5/1014 (0.5%) 1/1012 (0.1%)
    Intra-abdominal haematoma 2/1014 (0.2%) 1/1012 (0.1%)
    Intra-abdominal haemorrhage 1/1014 (0.1%) 0/1012 (0%)
    Large intestine perforation 1/1014 (0.1%) 0/1012 (0%)
    Large intestine polyp 1/1014 (0.1%) 0/1012 (0%)
    Lumbar hernia 0/1014 (0%) 1/1012 (0.1%)
    Mallory-Weiss syndrome 1/1014 (0.1%) 0/1012 (0%)
    Melaena 0/1014 (0%) 1/1012 (0.1%)
    Mouth ulceration 1/1014 (0.1%) 2/1012 (0.2%)
    Nausea 3/1014 (0.3%) 9/1012 (0.9%)
    Oesophageal achalasia 1/1014 (0.1%) 0/1012 (0%)
    Oesophageal spasm 0/1014 (0%) 1/1012 (0.1%)
    Oesophagitis 0/1014 (0%) 1/1012 (0.1%)
    Pancreatitis 1/1014 (0.1%) 2/1012 (0.2%)
    Pancreatitis acute 0/1014 (0%) 2/1012 (0.2%)
    Pancreatitis chronic 0/1014 (0%) 1/1012 (0.1%)
    Rectal haemorrhage 0/1014 (0%) 2/1012 (0.2%)
    Retching 0/1014 (0%) 1/1012 (0.1%)
    Retroperitoneal haematoma 2/1014 (0.2%) 5/1012 (0.5%)
    Retroperitoneal haemorrhage 0/1014 (0%) 1/1012 (0.1%)
    Salivary gland enlargement 1/1014 (0.1%) 0/1012 (0%)
    Small intestinal obstruction 2/1014 (0.2%) 4/1012 (0.4%)
    Stomatitis 0/1014 (0%) 2/1012 (0.2%)
    Umbilical hernia 3/1014 (0.3%) 0/1012 (0%)
    Volvulus 1/1014 (0.1%) 0/1012 (0%)
    Volvulus of small bowel 1/1014 (0.1%) 0/1012 (0%)
    Vomiting 6/1014 (0.6%) 13/1012 (1.3%)
    General disorders
    Asthenia 0/1014 (0%) 1/1012 (0.1%)
    Catheter site haemorrhage 1/1014 (0.1%) 0/1012 (0%)
    Chest discomfort 1/1014 (0.1%) 0/1012 (0%)
    Chest pain 1/1014 (0.1%) 2/1012 (0.2%)
    Chills 1/1014 (0.1%) 2/1012 (0.2%)
    Death 0/1014 (0%) 2/1012 (0.2%)
    Fatigue 2/1014 (0.2%) 2/1012 (0.2%)
    Gait inability 0/1014 (0%) 1/1012 (0.1%)
    General physical health deterioration 0/1014 (0%) 1/1012 (0.1%)
    Generalised oedema 1/1014 (0.1%) 0/1012 (0%)
    Hyperthermia 1/1014 (0.1%) 0/1012 (0%)
    Hypothermia 0/1014 (0%) 1/1012 (0.1%)
    Ill-defined disorder 0/1014 (0%) 1/1012 (0.1%)
    Impaired healing 10/1014 (1%) 1/1012 (0.1%)
    Malaise 2/1014 (0.2%) 1/1012 (0.1%)
    Medical device site discomfort 1/1014 (0.1%) 0/1012 (0%)
    Medical device site inflammation 1/1014 (0.1%) 0/1012 (0%)
    Microlithiasis 0/1014 (0%) 1/1012 (0.1%)
    Multiple organ dysfunction syndrome 1/1014 (0.1%) 0/1012 (0%)
    Non-cardiac chest pain 1/1014 (0.1%) 2/1012 (0.2%)
    Oedema peripheral 7/1014 (0.7%) 4/1012 (0.4%)
    Pain 0/1014 (0%) 1/1012 (0.1%)
    Peripheral swelling 0/1014 (0%) 2/1012 (0.2%)
    Pyrexia 35/1014 (3.5%) 36/1012 (3.6%)
    Sudden death 1/1014 (0.1%) 0/1012 (0%)
    Suprapubic pain 0/1014 (0%) 1/1012 (0.1%)
    Swelling 0/1014 (0%) 1/1012 (0.1%)
    Systemic inflammatory response syndrome 1/1014 (0.1%) 2/1012 (0.2%)
    Hepatobiliary disorders
    Bile duct stone 1/1014 (0.1%) 0/1012 (0%)
    Biliary colic 0/1014 (0%) 1/1012 (0.1%)
    Biliary dilatation 0/1014 (0%) 1/1012 (0.1%)
    Cholangitis 1/1014 (0.1%) 0/1012 (0%)
    Cholecystitis 2/1014 (0.2%) 3/1012 (0.3%)
    Cholecystitis acute 0/1014 (0%) 1/1012 (0.1%)
    Cholelithiasis 0/1014 (0%) 2/1012 (0.2%)
    Cholestasis 1/1014 (0.1%) 0/1012 (0%)
    Hepatocellular injury 0/1014 (0%) 1/1012 (0.1%)
    Perforation bile duct 0/1014 (0%) 1/1012 (0.1%)
    Immune system disorders
    Anaphylactic reaction 0/1014 (0%) 1/1012 (0.1%)
    Chronic allograft nephropathy 0/1014 (0%) 1/1012 (0.1%)
    Hypersensitivity 0/1014 (0%) 1/1012 (0.1%)
    Immunosuppression 1/1014 (0.1%) 0/1012 (0%)
    Kidney transplant rejection 18/1014 (1.8%) 17/1012 (1.7%)
    Renal transplant failure 4/1014 (0.4%) 5/1012 (0.5%)
    Transplant rejection 45/1014 (4.4%) 25/1012 (2.5%)
    Infections and infestations
    Abdominal abscess 1/1014 (0.1%) 1/1012 (0.1%)
    Abdominal infection 1/1014 (0.1%) 0/1012 (0%)
    Actinomycosis 1/1014 (0.1%) 0/1012 (0%)
    Adenoviral haemorrhagic cystitis 0/1014 (0%) 1/1012 (0.1%)
    Adenovirus infection 2/1014 (0.2%) 1/1012 (0.1%)
    Anal abscess 1/1014 (0.1%) 1/1012 (0.1%)
    Appendicitis 0/1014 (0%) 3/1012 (0.3%)
    Arteriovenous fistula site infection 0/1014 (0%) 1/1012 (0.1%)
    Arthritis bacterial 0/1014 (0%) 1/1012 (0.1%)
    Arthritis infective 1/1014 (0.1%) 0/1012 (0%)
    Asymptomatic bacteriuria 1/1014 (0.1%) 0/1012 (0%)
    Atypical pneumonia 2/1014 (0.2%) 0/1012 (0%)
    BK virus infection 3/1014 (0.3%) 5/1012 (0.5%)
    Bacteraemia 3/1014 (0.3%) 0/1012 (0%)
    Bacterial diarrhoea 0/1014 (0%) 1/1012 (0.1%)
    Bacterial infection 0/1014 (0%) 1/1012 (0.1%)
    Bacterial prostatitis 1/1014 (0.1%) 1/1012 (0.1%)
    Bacterial pyelonephritis 2/1014 (0.2%) 1/1012 (0.1%)
    Bacterial sepsis 1/1014 (0.1%) 1/1012 (0.1%)
    Bacteriuria 0/1014 (0%) 2/1012 (0.2%)
    Blister infected 0/1014 (0%) 1/1012 (0.1%)
    Bronchitis 2/1014 (0.2%) 3/1012 (0.3%)
    Bronchopulmonary aspergillosis 1/1014 (0.1%) 2/1012 (0.2%)
    Campylobacter gastroenteritis 1/1014 (0.1%) 0/1012 (0%)
    Candida infection 2/1014 (0.2%) 0/1012 (0%)
    Candiduria 0/1014 (0%) 1/1012 (0.1%)
    Cellulitis 5/1014 (0.5%) 6/1012 (0.6%)
    Chest wall abscess 0/1014 (0%) 1/1012 (0.1%)
    Chronic sinusitis 1/1014 (0.1%) 0/1012 (0%)
    Chronic tonsillitis 1/1014 (0.1%) 1/1012 (0.1%)
    Clostridium difficile colitis 4/1014 (0.4%) 3/1012 (0.3%)
    Clostridium difficile infection 1/1014 (0.1%) 0/1012 (0%)
    Corona virus infection 1/1014 (0.1%) 0/1012 (0%)
    Cryptococcosis 0/1014 (0%) 3/1012 (0.3%)
    Cystitis viral 1/1014 (0.1%) 0/1012 (0%)
    Cytomegalovirus colitis 0/1014 (0%) 9/1012 (0.9%)
    Cytomegalovirus enteritis 0/1014 (0%) 1/1012 (0.1%)
    Cytomegalovirus gastroenteritis 0/1014 (0%) 3/1012 (0.3%)
    Cytomegalovirus gastrointestinal infection 0/1014 (0%) 1/1012 (0.1%)
    Cytomegalovirus hepatitis 0/1014 (0%) 2/1012 (0.2%)
    Cytomegalovirus infection 6/1014 (0.6%) 48/1012 (4.7%)
    Dengue fever 1/1014 (0.1%) 0/1012 (0%)
    Dermatophytosis 1/1014 (0.1%) 0/1012 (0%)
    Device related infection 1/1014 (0.1%) 3/1012 (0.3%)
    Device related sepsis 1/1014 (0.1%) 0/1012 (0%)
    Diabetic foot infection 1/1014 (0.1%) 2/1012 (0.2%)
    Diarrhoea infectious 1/1014 (0.1%) 0/1012 (0%)
    Disseminated tuberculosis 1/1014 (0.1%) 0/1012 (0%)
    Diverticulitis 3/1014 (0.3%) 3/1012 (0.3%)
    Ear infection 1/1014 (0.1%) 0/1012 (0%)
    Encephalitis 1/1014 (0.1%) 0/1012 (0%)
    Endocarditis 1/1014 (0.1%) 1/1012 (0.1%)
    Enteritis infectious 1/1014 (0.1%) 0/1012 (0%)
    Enterococcal infection 1/1014 (0.1%) 1/1012 (0.1%)
    Enterococcal sepsis 1/1014 (0.1%) 0/1012 (0%)
    Enterocolitis viral 1/1014 (0.1%) 0/1012 (0%)
    Epididymitis 0/1014 (0%) 1/1012 (0.1%)
    Erysipelas 3/1014 (0.3%) 0/1012 (0%)
    Escherichia bacteraemia 0/1014 (0%) 2/1012 (0.2%)
    Escherichia infection 1/1014 (0.1%) 1/1012 (0.1%)
    Escherichia pyelonephritis 1/1014 (0.1%) 1/1012 (0.1%)
    Escherichia sepsis 5/1014 (0.5%) 1/1012 (0.1%)
    Escherichia urinary tract infection 1/1014 (0.1%) 7/1012 (0.7%)
    Febrile infection 1/1014 (0.1%) 1/1012 (0.1%)
    Fungal infection 1/1014 (0.1%) 1/1012 (0.1%)
    Fungal sepsis 0/1014 (0%) 2/1012 (0.2%)
    Gangrene 1/1014 (0.1%) 2/1012 (0.2%)
    Gastroenteritis 18/1014 (1.8%) 23/1012 (2.3%)
    Gastroenteritis clostridial 0/1014 (0%) 1/1012 (0.1%)
    Gastroenteritis cryptosporidial 0/1014 (0%) 1/1012 (0.1%)
    Gastroenteritis norovirus 0/1014 (0%) 6/1012 (0.6%)
    Gastroenteritis viral 1/1014 (0.1%) 3/1012 (0.3%)
    Gastrointestinal infection 2/1014 (0.2%) 1/1012 (0.1%)
    Groin abscess 3/1014 (0.3%) 2/1012 (0.2%)
    HIV infection 0/1014 (0%) 1/1012 (0.1%)
    Haematoma infection 2/1014 (0.2%) 0/1012 (0%)
    Hepatic cyst infection 1/1014 (0.1%) 0/1012 (0%)
    Hepatitis C 0/1014 (0%) 1/1012 (0.1%)
    Hepatitis E 0/1014 (0%) 1/1012 (0.1%)
    Hepatitis viral 0/1014 (0%) 1/1012 (0.1%)
    Herpes simplex 1/1014 (0.1%) 1/1012 (0.1%)
    Herpes simplex pneumonia 1/1014 (0.1%) 0/1012 (0%)
    Herpes zoster 5/1014 (0.5%) 4/1012 (0.4%)
    Herpes zoster disseminated 0/1014 (0%) 1/1012 (0.1%)
    Ileal gangrene 0/1014 (0%) 1/1012 (0.1%)
    Infected lymphocele 4/1014 (0.4%) 1/1012 (0.1%)
    Infected seroma 1/1014 (0.1%) 1/1012 (0.1%)
    Infected skin ulcer 3/1014 (0.3%) 2/1012 (0.2%)
    Infection 2/1014 (0.2%) 1/1012 (0.1%)
    Infectious colitis 0/1014 (0%) 1/1012 (0.1%)
    Infectious pleural effusion 1/1014 (0.1%) 0/1012 (0%)
    Influenza 6/1014 (0.6%) 5/1012 (0.5%)
    Intervertebral discitis 0/1014 (0%) 2/1012 (0.2%)
    Intestinal sepsis 1/1014 (0.1%) 0/1012 (0%)
    Kidney infection 1/1014 (0.1%) 2/1012 (0.2%)
    Klebsiella bacteraemia 0/1014 (0%) 1/1012 (0.1%)
    Klebsiella sepsis 2/1014 (0.2%) 0/1012 (0%)
    Lower respiratory tract infection 1/1014 (0.1%) 3/1012 (0.3%)
    Lung infection 1/1014 (0.1%) 2/1012 (0.2%)
    Medical device site cellulitis 1/1014 (0.1%) 0/1012 (0%)
    Medical device site infection 0/1014 (0%) 1/1012 (0.1%)
    Meningitis bacterial 1/1014 (0.1%) 0/1012 (0%)
    Meningitis cryptococcal 1/1014 (0.1%) 0/1012 (0%)
    Nasopharyngitis 1/1014 (0.1%) 1/1012 (0.1%)
    Neutropenic sepsis 0/1014 (0%) 1/1012 (0.1%)
    Nocardiosis 0/1014 (0%) 1/1012 (0.1%)
    Oral candidiasis 0/1014 (0%) 2/1012 (0.2%)
    Oral herpes 1/1014 (0.1%) 1/1012 (0.1%)
    Orchitis 1/1014 (0.1%) 3/1012 (0.3%)
    Osteomyelitis 5/1014 (0.5%) 2/1012 (0.2%)
    Osteomyelitis chronic 2/1014 (0.2%) 0/1012 (0%)
    Parvovirus B19 infection 1/1014 (0.1%) 0/1012 (0%)
    Perinephric abscess 2/1014 (0.2%) 0/1012 (0%)
    Peritonitis 1/1014 (0.1%) 0/1012 (0%)
    Peritonsillar abscess 1/1014 (0.1%) 1/1012 (0.1%)
    Pharyngotonsillitis 0/1014 (0%) 1/1012 (0.1%)
    Pneumococcal sepsis 1/1014 (0.1%) 0/1012 (0%)
    Pneumocystis jirovecii pneumonia 6/1014 (0.6%) 3/1012 (0.3%)
    Pneumonia 55/1014 (5.4%) 36/1012 (3.6%)
    Pneumonia bacterial 1/1014 (0.1%) 1/1012 (0.1%)
    Pneumonia cryptococcal 0/1014 (0%) 2/1012 (0.2%)
    Pneumonia cytomegaloviral 1/1014 (0.1%) 4/1012 (0.4%)
    Pneumonia fungal 0/1014 (0%) 1/1012 (0.1%)
    Pneumonia haemophilus 0/1014 (0%) 1/1012 (0.1%)
    Pneumonia influenzal 1/1014 (0.1%) 0/1012 (0%)
    Pneumonia legionella 1/1014 (0.1%) 1/1012 (0.1%)
    Polyomavirus-associated nephropathy 4/1014 (0.4%) 10/1012 (1%)
    Postoperative abscess 0/1014 (0%) 1/1012 (0.1%)
    Postoperative wound infection 3/1014 (0.3%) 3/1012 (0.3%)
    Pseudomembranous colitis 0/1014 (0%) 1/1012 (0.1%)
    Pseudomonal bacteraemia 0/1014 (0%) 1/1012 (0.1%)
    Pseudomonal sepsis 0/1014 (0%) 1/1012 (0.1%)
    Pulmonary tuberculosis 2/1014 (0.2%) 1/1012 (0.1%)
    Pyelonephritis 24/1014 (2.4%) 33/1012 (3.3%)
    Pyelonephritis acute 6/1014 (0.6%) 13/1012 (1.3%)
    Pyelonephritis chronic 1/1014 (0.1%) 1/1012 (0.1%)
    Pyuria 0/1014 (0%) 1/1012 (0.1%)
    Renal cyst infection 1/1014 (0.1%) 3/1012 (0.3%)
    Renal graft infection 2/1014 (0.2%) 0/1012 (0%)
    Respiratory tract infection 5/1014 (0.5%) 5/1012 (0.5%)
    Respiratory tract infection fungal 0/1014 (0%) 1/1012 (0.1%)
    Respiratory tract infection viral 0/1014 (0%) 1/1012 (0.1%)
    Rhinitis 1/1014 (0.1%) 0/1012 (0%)
    Rhinovirus infection 0/1014 (0%) 1/1012 (0.1%)
    Salmonellosis 0/1014 (0%) 1/1012 (0.1%)
    Sepsis 20/1014 (2%) 7/1012 (0.7%)
    Septic shock 6/1014 (0.6%) 8/1012 (0.8%)
    Sinusitis 1/1014 (0.1%) 1/1012 (0.1%)
    Sinusitis fungal 0/1014 (0%) 1/1012 (0.1%)
    Staphylococcal bacteraemia 1/1014 (0.1%) 1/1012 (0.1%)
    Streptococcal sepsis 1/1014 (0.1%) 0/1012 (0%)
    Subcutaneous abscess 2/1014 (0.2%) 0/1012 (0%)
    Systemic candida 0/1014 (0%) 1/1012 (0.1%)
    Tonsillitis bacterial 1/1014 (0.1%) 0/1012 (0%)
    Tooth abscess 0/1014 (0%) 1/1012 (0.1%)
    Tracheobronchitis 1/1014 (0.1%) 1/1012 (0.1%)
    Transplant abscess 1/1014 (0.1%) 0/1012 (0%)
    Tuberculosis 1/1014 (0.1%) 0/1012 (0%)
    Tuberculosis gastrointestinal 0/1014 (0%) 1/1012 (0.1%)
    Upper respiratory tract infection 5/1014 (0.5%) 4/1012 (0.4%)
    Urinary tract infection 78/1014 (7.7%) 93/1012 (9.2%)
    Urinary tract infection bacterial 4/1014 (0.4%) 1/1012 (0.1%)
    Urinary tract infection enterococcal 1/1014 (0.1%) 0/1012 (0%)
    Urinary tract infection fungal 0/1014 (0%) 1/1012 (0.1%)
    Urosepsis 23/1014 (2.3%) 23/1012 (2.3%)
    Varicella 0/1014 (0%) 1/1012 (0.1%)
    Viral diarrhoea 1/1014 (0.1%) 1/1012 (0.1%)
    Viral infection 2/1014 (0.2%) 2/1012 (0.2%)
    Viral myocarditis 0/1014 (0%) 1/1012 (0.1%)
    Viral upper respiratory tract infection 1/1014 (0.1%) 1/1012 (0.1%)
    Vulvovaginal mycotic infection 0/1014 (0%) 1/1012 (0.1%)
    Wound abscess 1/1014 (0.1%) 0/1012 (0%)
    Wound infection 5/1014 (0.5%) 4/1012 (0.4%)
    Injury, poisoning and procedural complications
    Accidental overdose 1/1014 (0.1%) 0/1012 (0%)
    Anaemia postoperative 1/1014 (0.1%) 0/1012 (0%)
    Anaesthetic complication 1/1014 (0.1%) 0/1012 (0%)
    Anastomotic haemorrhage 1/1014 (0.1%) 0/1012 (0%)
    Ankle fracture 1/1014 (0.1%) 0/1012 (0%)
    Aponeurosis contusion 0/1014 (0%) 3/1012 (0.3%)
    Arterial injury 1/1014 (0.1%) 0/1012 (0%)
    Arteriovenous fistula aneurysm 1/1014 (0.1%) 3/1012 (0.3%)
    Arteriovenous fistula site complication 1/1014 (0.1%) 4/1012 (0.4%)
    Arteriovenous fistula thrombosis 2/1014 (0.2%) 1/1012 (0.1%)
    Avulsion fracture 1/1014 (0.1%) 0/1012 (0%)
    Complications of transplant surgery 1/1014 (0.1%) 1/1012 (0.1%)
    Complications of transplanted kidney 34/1014 (3.4%) 28/1012 (2.8%)
    Contusion 0/1014 (0%) 1/1012 (0.1%)
    Coronary bypass stenosis 0/1014 (0%) 1/1012 (0.1%)
    Delayed graft function 7/1014 (0.7%) 2/1012 (0.2%)
    Fall 1/1014 (0.1%) 1/1012 (0.1%)
    Femoral neck fracture 2/1014 (0.2%) 1/1012 (0.1%)
    Femur fracture 2/1014 (0.2%) 0/1012 (0%)
    Forearm fracture 0/1014 (0%) 1/1012 (0.1%)
    Graft complication 2/1014 (0.2%) 3/1012 (0.3%)
    Graft haemorrhage 1/1014 (0.1%) 1/1012 (0.1%)
    Graft loss 16/1014 (1.6%) 12/1012 (1.2%)
    Graft thrombosis 2/1014 (0.2%) 0/1012 (0%)
    Humerus fracture 1/1014 (0.1%) 1/1012 (0.1%)
    Incision site complication 0/1014 (0%) 1/1012 (0.1%)
    Incisional hernia 8/1014 (0.8%) 1/1012 (0.1%)
    Injury 1/1014 (0.1%) 0/1012 (0%)
    Joint dislocation 1/1014 (0.1%) 0/1012 (0%)
    Laceration 1/1014 (0.1%) 0/1012 (0%)
    Limb injury 0/1014 (0%) 1/1012 (0.1%)
    Lower limb fracture 1/1014 (0.1%) 0/1012 (0%)
    Lumbar vertebral fracture 0/1014 (0%) 1/1012 (0.1%)
    Muscle strain 0/1014 (0%) 1/1012 (0.1%)
    Musculoskeletal injury 0/1014 (0%) 1/1012 (0.1%)
    Overdose 0/1014 (0%) 3/1012 (0.3%)
    Pelvic fracture 1/1014 (0.1%) 0/1012 (0%)
    Peripheral arterial reocclusion 0/1014 (0%) 1/1012 (0.1%)
    Perirenal haematoma 1/1014 (0.1%) 1/1012 (0.1%)
    Post procedural complication 3/1014 (0.3%) 1/1012 (0.1%)
    Post procedural discharge 0/1014 (0%) 1/1012 (0.1%)
    Post procedural haematoma 3/1014 (0.3%) 1/1012 (0.1%)
    Post procedural haematuria 2/1014 (0.2%) 1/1012 (0.1%)
    Post procedural haemorrhage 4/1014 (0.4%) 4/1012 (0.4%)
    Post procedural persistent drain fluid 1/1014 (0.1%) 1/1012 (0.1%)
    Post procedural urine leak 0/1014 (0%) 1/1012 (0.1%)
    Postoperative fever 1/1014 (0.1%) 0/1012 (0%)
    Postoperative hernia 2/1014 (0.2%) 1/1012 (0.1%)
    Procedural haemorrhage 1/1014 (0.1%) 1/1012 (0.1%)
    Radius fracture 1/1014 (0.1%) 2/1012 (0.2%)
    Renal lymphocele 3/1014 (0.3%) 1/1012 (0.1%)
    Renal transplant torsion 1/1014 (0.1%) 0/1012 (0%)
    Rib fracture 1/1014 (0.1%) 1/1012 (0.1%)
    Scar 1/1014 (0.1%) 0/1012 (0%)
    Scrotal haematoma 0/1014 (0%) 2/1012 (0.2%)
    Seroma 5/1014 (0.5%) 2/1012 (0.2%)
    Shunt aneurysm 2/1014 (0.2%) 1/1012 (0.1%)
    Shunt stenosis 2/1014 (0.2%) 0/1012 (0%)
    Spinal fracture 1/1014 (0.1%) 0/1012 (0%)
    Stress fracture 1/1014 (0.1%) 0/1012 (0%)
    Subarachnoid haemorrhage 2/1014 (0.2%) 1/1012 (0.1%)
    Subcutaneous haematoma 1/1014 (0.1%) 0/1012 (0%)
    Tendon rupture 2/1014 (0.2%) 3/1012 (0.3%)
    Tibia fracture 0/1014 (0%) 2/1012 (0.2%)
    Toxicity to various agents 5/1014 (0.5%) 4/1012 (0.4%)
    Transplant dysfunction 7/1014 (0.7%) 7/1012 (0.7%)
    Transplant failure 1/1014 (0.1%) 1/1012 (0.1%)
    Transplantation complication 5/1014 (0.5%) 1/1012 (0.1%)
    Traumatic fracture 1/1014 (0.1%) 0/1012 (0%)
    Ulna fracture 1/1014 (0.1%) 0/1012 (0%)
    Upper limb fracture 0/1014 (0%) 1/1012 (0.1%)
    Ureteric anastomosis complication 1/1014 (0.1%) 1/1012 (0.1%)
    Urinary anastomotic leak 1/1014 (0.1%) 1/1012 (0.1%)
    Vaccination complication 1/1014 (0.1%) 0/1012 (0%)
    Vascular graft complication 1/1014 (0.1%) 1/1012 (0.1%)
    Vascular graft stenosis 0/1014 (0%) 1/1012 (0.1%)
    Vascular graft thrombosis 1/1014 (0.1%) 0/1012 (0%)
    Vascular pseudoaneurysm 1/1014 (0.1%) 0/1012 (0%)
    Wound decomposition 1/1014 (0.1%) 0/1012 (0%)
    Wound dehiscence 10/1014 (1%) 3/1012 (0.3%)
    Wound secretion 1/1014 (0.1%) 0/1012 (0%)
    Wrist fracture 0/1014 (0%) 1/1012 (0.1%)
    Investigations
    Alanine aminotransferase increased 0/1014 (0%) 1/1012 (0.1%)
    Anticoagulation drug level above therapeutic 1/1014 (0.1%) 0/1012 (0%)
    Aspartate aminotransferase increased 0/1014 (0%) 1/1012 (0.1%)
    Biopsy kidney 1/1014 (0.1%) 0/1012 (0%)
    Blood creatine increased 2/1014 (0.2%) 3/1012 (0.3%)
    Blood creatinine abnormal 1/1014 (0.1%) 2/1012 (0.2%)
    Blood creatinine increased 50/1014 (4.9%) 36/1012 (3.6%)
    Blood glucose increased 1/1014 (0.1%) 0/1012 (0%)
    Blood phosphorus decreased 0/1014 (0%) 1/1012 (0.1%)
    Blood urea increased 1/1014 (0.1%) 0/1012 (0%)
    C-reactive protein increased 2/1014 (0.2%) 0/1012 (0%)
    Catheterisation cardiac 1/1014 (0.1%) 0/1012 (0%)
    Ejection fraction abnormal 0/1014 (0%) 1/1012 (0.1%)
    Electrocardiogram T wave inversion 0/1014 (0%) 1/1012 (0.1%)
    Haemoglobin decreased 0/1014 (0%) 1/1012 (0.1%)
    Haptoglobin decreased 1/1014 (0.1%) 0/1012 (0%)
    Immunosuppressant drug level increased 1/1014 (0.1%) 0/1012 (0%)
    Inflammatory marker increased 1/1014 (0.1%) 2/1012 (0.2%)
    Liver function test increased 1/1014 (0.1%) 0/1012 (0%)
    Norovirus test positive 1/1014 (0.1%) 0/1012 (0%)
    Occult blood positive 1/1014 (0.1%) 0/1012 (0%)
    Polyomavirus test positive 0/1014 (0%) 1/1012 (0.1%)
    Transaminases increased 0/1014 (0%) 1/1012 (0.1%)
    Troponin increased 0/1014 (0%) 1/1012 (0.1%)
    Urine output decreased 3/1014 (0.3%) 0/1012 (0%)
    Weight decreased 0/1014 (0%) 1/1012 (0.1%)
    Metabolism and nutrition disorders
    Cachexia 0/1014 (0%) 2/1012 (0.2%)
    Calciphylaxis 1/1014 (0.1%) 0/1012 (0%)
    Decreased appetite 2/1014 (0.2%) 2/1012 (0.2%)
    Dehydration 6/1014 (0.6%) 11/1012 (1.1%)
    Diabetes mellitus 9/1014 (0.9%) 10/1012 (1%)
    Diabetes mellitus inadequate control 1/1014 (0.1%) 2/1012 (0.2%)
    Diabetic ketoacidosis 3/1014 (0.3%) 2/1012 (0.2%)
    Electrolyte imbalance 1/1014 (0.1%) 0/1012 (0%)
    Fluid overload 5/1014 (0.5%) 3/1012 (0.3%)
    Fluid retention 1/1014 (0.1%) 0/1012 (0%)
    Gout 1/1014 (0.1%) 1/1012 (0.1%)
    Hypercalcaemia 0/1014 (0%) 1/1012 (0.1%)
    Hyperglycaemia 5/1014 (0.5%) 6/1012 (0.6%)
    Hyperkalaemia 11/1014 (1.1%) 10/1012 (1%)
    Hyperlipidaemia 1/1014 (0.1%) 0/1012 (0%)
    Hypertriglyceridaemia 1/1014 (0.1%) 0/1012 (0%)
    Hypervolaemia 0/1014 (0%) 1/1012 (0.1%)
    Hypocalcaemia 2/1014 (0.2%) 1/1012 (0.1%)
    Hypoglycaemia 0/1014 (0%) 5/1012 (0.5%)
    Hypokalaemia 3/1014 (0.3%) 0/1012 (0%)
    Hypomagnesaemia 0/1014 (0%) 1/1012 (0.1%)
    Hyponatraemia 1/1014 (0.1%) 5/1012 (0.5%)
    Hypophosphataemia 0/1014 (0%) 1/1012 (0.1%)
    Hypovolaemia 0/1014 (0%) 1/1012 (0.1%)
    Iron deficiency 0/1014 (0%) 1/1012 (0.1%)
    Malnutrition 0/1014 (0%) 1/1012 (0.1%)
    Metabolic acidosis 0/1014 (0%) 4/1012 (0.4%)
    Type 1 diabetes mellitus 0/1014 (0%) 1/1012 (0.1%)
    Musculoskeletal and connective tissue disorders
    Arthralgia 2/1014 (0.2%) 2/1012 (0.2%)
    Back pain 3/1014 (0.3%) 1/1012 (0.1%)
    Flank pain 0/1014 (0%) 1/1012 (0.1%)
    Gouty arthritis 0/1014 (0%) 2/1012 (0.2%)
    Groin pain 0/1014 (0%) 1/1012 (0.1%)
    Intervertebral disc protrusion 2/1014 (0.2%) 1/1012 (0.1%)
    Intervertebral disc space narrowing 0/1014 (0%) 1/1012 (0.1%)
    Lumbar spinal stenosis 0/1014 (0%) 1/1012 (0.1%)
    Muscular weakness 2/1014 (0.2%) 2/1012 (0.2%)
    Musculoskeletal pain 1/1014 (0.1%) 1/1012 (0.1%)
    Myalgia intercostal 1/1014 (0.1%) 0/1012 (0%)
    Osteitis 0/1014 (0%) 2/1012 (0.2%)
    Osteoarthritis 4/1014 (0.4%) 2/1012 (0.2%)
    Osteonecrosis 9/1014 (0.9%) 1/1012 (0.1%)
    Pain in extremity 0/1014 (0%) 1/1012 (0.1%)
    Pubic pain 1/1014 (0.1%) 0/1012 (0%)
    Sacroiliitis 1/1014 (0.1%) 0/1012 (0%)
    Spinal column stenosis 0/1014 (0%) 1/1012 (0.1%)
    Spinal osteoarthritis 0/1014 (0%) 1/1012 (0.1%)
    Synovial cyst 1/1014 (0.1%) 0/1012 (0%)
    Tendonitis 0/1014 (0%) 1/1012 (0.1%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Adenocarcinoma gastric 1/1014 (0.1%) 0/1012 (0%)
    Adenocarcinoma pancreas 0/1014 (0%) 1/1012 (0.1%)
    Basal cell carcinoma 10/1014 (1%) 4/1012 (0.4%)
    Benign gastrointestinal neoplasm 0/1014 (0%) 1/1012 (0.1%)
    Benign neoplasm of thyroid gland 1/1014 (0.1%) 0/1012 (0%)
    Benign pancreatic neoplasm 0/1014 (0%) 1/1012 (0.1%)
    Bladder cancer 0/1014 (0%) 1/1012 (0.1%)
    Bowen's disease 1/1014 (0.1%) 0/1012 (0%)
    Brain neoplasm 0/1014 (0%) 1/1012 (0.1%)
    Breast cancer 0/1014 (0%) 3/1012 (0.3%)
    Bronchioloalveolar carcinoma 0/1014 (0%) 1/1012 (0.1%)
    Cerebral haemangioma 0/1014 (0%) 1/1012 (0.1%)
    Clear cell renal cell carcinoma 1/1014 (0.1%) 0/1012 (0%)
    Epstein-Barr virus associated lymphoma 0/1014 (0%) 1/1012 (0.1%)
    Gastric cancer 1/1014 (0.1%) 0/1012 (0%)
    Leydig cell tumour of the testis 0/1014 (0%) 1/1012 (0.1%)
    Lipoma 0/1014 (0%) 1/1012 (0.1%)
    Lung adenocarcinoma 0/1014 (0%) 1/1012 (0.1%)
    Lymphoproliferative disorder 0/1014 (0%) 1/1012 (0.1%)
    Malignant melanoma 4/1014 (0.4%) 1/1012 (0.1%)
    Malignant neoplasm of pleura metastatic 1/1014 (0.1%) 0/1012 (0%)
    Metastases to bone 1/1014 (0.1%) 0/1012 (0%)
    Metastases to lymph nodes 1/1014 (0.1%) 0/1012 (0%)
    Metastases to peritoneum 1/1014 (0.1%) 0/1012 (0%)
    Metastases to spine 0/1014 (0%) 1/1012 (0.1%)
    Metastatic squamous cell carcinoma 1/1014 (0.1%) 0/1012 (0%)
    Monoclonal gammopathy 1/1014 (0.1%) 0/1012 (0%)
    Neoplasm malignant 0/1014 (0%) 1/1012 (0.1%)
    Non-small cell lung cancer 0/1014 (0%) 1/1012 (0.1%)
    Oesophageal adenocarcinoma 0/1014 (0%) 1/1012 (0.1%)
    Papillary tumour of renal pelvis 0/1014 (0%) 1/1012 (0.1%)
    Plasmacytoma 0/1014 (0%) 1/1012 (0.1%)
    Polycythaemia vera 1/1014 (0.1%) 0/1012 (0%)
    Post transplant lymphoproliferative disorder 0/1014 (0%) 2/1012 (0.2%)
    Prostate cancer 3/1014 (0.3%) 0/1012 (0%)
    Renal cancer 2/1014 (0.2%) 1/1012 (0.1%)
    Renal cell carcinoma 1/1014 (0.1%) 1/1012 (0.1%)
    Salivary gland cancer 0/1014 (0%) 1/1012 (0.1%)
    Skin cancer 0/1014 (0%) 1/1012 (0.1%)
    Squamous cell carcinoma 8/1014 (0.8%) 4/1012 (0.4%)
    Squamous cell carcinoma of skin 0/1014 (0%) 5/1012 (0.5%)
    Testicular neoplasm 1/1014 (0.1%) 0/1012 (0%)
    Tumour of ampulla of Vater 0/1014 (0%) 1/1012 (0.1%)
    Uterine leiomyoma 1/1014 (0.1%) 0/1012 (0%)
    Nervous system disorders
    Ataxia 0/1014 (0%) 1/1012 (0.1%)
    Autoimmune encephalopathy 0/1014 (0%) 1/1012 (0.1%)
    Brain injury 1/1014 (0.1%) 0/1012 (0%)
    Brain stem infarction 0/1014 (0%) 1/1012 (0.1%)
    Central nervous system lesion 0/1014 (0%) 1/1012 (0.1%)
    Cerebellar stroke 0/1014 (0%) 1/1012 (0.1%)
    Cerebral haemorrhage 1/1014 (0.1%) 1/1012 (0.1%)
    Cerebral infarction 1/1014 (0.1%) 0/1012 (0%)
    Cerebral ischaemia 1/1014 (0.1%) 0/1012 (0%)
    Cerebrovascular accident 0/1014 (0%) 2/1012 (0.2%)
    Coma 1/1014 (0.1%) 0/1012 (0%)
    Dizziness 2/1014 (0.2%) 3/1012 (0.3%)
    Encephalopathy 0/1014 (0%) 1/1012 (0.1%)
    Headache 3/1014 (0.3%) 7/1012 (0.7%)
    Hyponatraemic seizure 1/1014 (0.1%) 0/1012 (0%)
    Hypotonia 1/1014 (0.1%) 0/1012 (0%)
    Hypoxic-ischaemic encephalopathy 0/1014 (0%) 1/1012 (0.1%)
    Ischaemic stroke 0/1014 (0%) 1/1012 (0.1%)
    Metabolic encephalopathy 1/1014 (0.1%) 0/1012 (0%)
    Migraine 0/1014 (0%) 1/1012 (0.1%)
    Myelitis transverse 0/1014 (0%) 1/1012 (0.1%)
    Neuropathy peripheral 0/1014 (0%) 1/1012 (0.1%)
    Neurotoxicity 1/1014 (0.1%) 2/1012 (0.2%)
    Presyncope 1/1014 (0.1%) 0/1012 (0%)
    Sciatica 1/1014 (0.1%) 0/1012 (0%)
    Seizure 1/1014 (0.1%) 0/1012 (0%)
    Spinal cord compression 0/1014 (0%) 1/1012 (0.1%)
    Syncope 1/1014 (0.1%) 3/1012 (0.3%)
    Transient ischaemic attack 0/1014 (0%) 1/1012 (0.1%)
    Transverse sinus thrombosis 0/1014 (0%) 1/1012 (0.1%)
    Tremor 2/1014 (0.2%) 1/1012 (0.1%)
    Visual field defect 1/1014 (0.1%) 0/1012 (0%)
    Pregnancy, puerperium and perinatal conditions
    Cephalhaematoma 0/1014 (0%) 1/1012 (0.1%)
    Product Issues
    Device dislocation 2/1014 (0.2%) 1/1012 (0.1%)
    Device leakage 0/1014 (0%) 1/1012 (0.1%)
    Device malfunction 0/1014 (0%) 1/1012 (0.1%)
    Psychiatric disorders
    Acute psychosis 1/1014 (0.1%) 0/1012 (0%)
    Aggression 0/1014 (0%) 1/1012 (0.1%)
    Anxiety 1/1014 (0.1%) 0/1012 (0%)
    Depression 0/1014 (0%) 1/1012 (0.1%)
    Hallucination, visual 0/1014 (0%) 1/1012 (0.1%)
    Mental disorder 0/1014 (0%) 1/1012 (0.1%)
    Mental status changes 1/1014 (0.1%) 2/1012 (0.2%)
    Post-traumatic stress disorder 0/1014 (0%) 1/1012 (0.1%)
    Psychotic disorder 0/1014 (0%) 1/1012 (0.1%)
    Suicide attempt 0/1014 (0%) 1/1012 (0.1%)
    Renal and urinary disorders
    Acute kidney injury 46/1014 (4.5%) 37/1012 (3.7%)
    Anuria 1/1014 (0.1%) 1/1012 (0.1%)
    Bladder neck obstruction 1/1014 (0.1%) 0/1012 (0%)
    Bladder obstruction 1/1014 (0.1%) 0/1012 (0%)
    Bladder perforation 0/1014 (0%) 1/1012 (0.1%)
    Calculus urinary 0/1014 (0%) 2/1012 (0.2%)
    Chronic kidney disease 1/1014 (0.1%) 0/1012 (0%)
    Cystitis haemorrhagic 1/1014 (0.1%) 0/1012 (0%)
    Diabetic nephropathy 0/1014 (0%) 1/1012 (0.1%)
    Dysuria 1/1014 (0.1%) 5/1012 (0.5%)
    End stage renal disease 1/1014 (0.1%) 0/1012 (0%)
    Focal segmental glomerulosclerosis 1/1014 (0.1%) 3/1012 (0.3%)
    Glomerulonephritis 1/1014 (0.1%) 2/1012 (0.2%)
    Glomerulonephritis chronic 1/1014 (0.1%) 0/1012 (0%)
    Glomerulonephritis membranoproliferative 1/1014 (0.1%) 1/1012 (0.1%)
    Glomerulonephritis membranous 1/1014 (0.1%) 1/1012 (0.1%)
    Glycosuria 0/1014 (0%) 1/1012 (0.1%)
    Haematuria 9/1014 (0.9%) 14/1012 (1.4%)
    Haemorrhage urinary tract 0/1014 (0%) 1/1012 (0.1%)
    Hydronephrosis 9/1014 (0.9%) 6/1012 (0.6%)
    Hydroureter 1/1014 (0.1%) 0/1012 (0%)
    Hypertonic bladder 0/1014 (0%) 1/1012 (0.1%)
    IgM nephropathy 1/1014 (0.1%) 0/1012 (0%)
    Ischaemic nephropathy 0/1014 (0%) 1/1012 (0.1%)
    Leukocyturia 0/1014 (0%) 1/1012 (0.1%)
    Mesangioproliferative glomerulonephritis 1/1014 (0.1%) 0/1012 (0%)
    Nephritis 1/1014 (0.1%) 0/1012 (0%)
    Nephrolithiasis 0/1014 (0%) 1/1012 (0.1%)
    Nephropathy 0/1014 (0%) 1/1012 (0.1%)
    Nephropathy toxic 1/1014 (0.1%) 0/1012 (0%)
    Nephrotic syndrome 0/1014 (0%) 1/1012 (0.1%)
    Obstructive nephropathy 1/1014 (0.1%) 1/1012 (0.1%)
    Oliguria 2/1014 (0.2%) 0/1012 (0%)
    Pelvi-ureteric obstruction 1/1014 (0.1%) 0/1012 (0%)
    Perinephric collection 2/1014 (0.2%) 5/1012 (0.5%)
    Pollakiuria 2/1014 (0.2%) 0/1012 (0%)
    Prerenal failure 0/1014 (0%) 1/1012 (0.1%)
    Proteinuria 15/1014 (1.5%) 3/1012 (0.3%)
    Pyelocaliectasis 2/1014 (0.2%) 1/1012 (0.1%)
    Renal artery dissection 1/1014 (0.1%) 0/1012 (0%)
    Renal artery occlusion 0/1014 (0%) 1/1012 (0.1%)
    Renal artery stenosis 4/1014 (0.4%) 7/1012 (0.7%)
    Renal artery thrombosis 1/1014 (0.1%) 2/1012 (0.2%)
    Renal cortical necrosis 1/1014 (0.1%) 0/1012 (0%)
    Renal cyst 0/1014 (0%) 1/1012 (0.1%)
    Renal cyst haemorrhage 2/1014 (0.2%) 1/1012 (0.1%)
    Renal cyst ruptured 0/1014 (0%) 1/1012 (0.1%)
    Renal failure 1/1014 (0.1%) 3/1012 (0.3%)
    Renal haematoma 1/1014 (0.1%) 1/1012 (0.1%)
    Renal impairment 23/1014 (2.3%) 25/1012 (2.5%)
    Renal ischaemia 0/1014 (0%) 1/1012 (0.1%)
    Renal necrosis 0/1014 (0%) 1/1012 (0.1%)
    Renal tubular atrophy 1/1014 (0.1%) 1/1012 (0.1%)
    Renal tubular necrosis 3/1014 (0.3%) 5/1012 (0.5%)
    Renal vein thrombosis 2/1014 (0.2%) 1/1012 (0.1%)
    Tubulointerstitial nephritis 0/1014 (0%) 1/1012 (0.1%)
    Ureteric dilatation 1/1014 (0.1%) 1/1012 (0.1%)
    Ureteric obstruction 3/1014 (0.3%) 1/1012 (0.1%)
    Ureteric stenosis 3/1014 (0.3%) 6/1012 (0.6%)
    Urethral obstruction 1/1014 (0.1%) 1/1012 (0.1%)
    Urethral stenosis 2/1014 (0.2%) 1/1012 (0.1%)
    Urge incontinence 0/1014 (0%) 1/1012 (0.1%)
    Urinary bladder haemorrhage 1/1014 (0.1%) 0/1012 (0%)
    Urinary bladder polyp 0/1014 (0%) 1/1012 (0.1%)
    Urinary fistula 3/1014 (0.3%) 2/1012 (0.2%)
    Urinary incontinence 9/1014 (0.9%) 1/1012 (0.1%)
    Urinary retention 1/1014 (0.1%) 8/1012 (0.8%)
    Urinary tract obstruction 2/1014 (0.2%) 4/1012 (0.4%)
    Urinoma 1/1014 (0.1%) 0/1012 (0%)
    Vesicoureteric reflux 1/1014 (0.1%) 0/1012 (0%)
    Reproductive system and breast disorders
    Acquired hydrocele 0/1014 (0%) 1/1012 (0.1%)
    Benign prostatic hyperplasia 2/1014 (0.2%) 3/1012 (0.3%)
    Cervical dysplasia 1/1014 (0.1%) 0/1012 (0%)
    Endometriosis 1/1014 (0.1%) 0/1012 (0%)
    Erectile dysfunction 1/1014 (0.1%) 0/1012 (0%)
    Menorrhagia 1/1014 (0.1%) 0/1012 (0%)
    Ovarian cyst ruptured 1/1014 (0.1%) 0/1012 (0%)
    Prostatitis 3/1014 (0.3%) 4/1012 (0.4%)
    Scrotal oedema 1/1014 (0.1%) 0/1012 (0%)
    Testicular oedema 1/1014 (0.1%) 0/1012 (0%)
    Respiratory, thoracic and mediastinal disorders
    Acute pulmonary oedema 2/1014 (0.2%) 2/1012 (0.2%)
    Acute respiratory failure 2/1014 (0.2%) 4/1012 (0.4%)
    Asthma 1/1014 (0.1%) 1/1012 (0.1%)
    Asthmatic crisis 0/1014 (0%) 1/1012 (0.1%)
    Bronchospasm 0/1014 (0%) 1/1012 (0.1%)
    Cough 0/1014 (0%) 2/1012 (0.2%)
    Dyspnoea 8/1014 (0.8%) 7/1012 (0.7%)
    Dyspnoea exertional 1/1014 (0.1%) 1/1012 (0.1%)
    Epistaxis 1/1014 (0.1%) 0/1012 (0%)
    Haemoptysis 2/1014 (0.2%) 2/1012 (0.2%)
    Hyperventilation 1/1014 (0.1%) 0/1012 (0%)
    Hypoxia 1/1014 (0.1%) 2/1012 (0.2%)
    Interstitial lung disease 1/1014 (0.1%) 0/1012 (0%)
    Lung disorder 2/1014 (0.2%) 0/1012 (0%)
    Lung infiltration 0/1014 (0%) 1/1012 (0.1%)
    Pleural effusion 1/1014 (0.1%) 0/1012 (0%)
    Pleurisy 1/1014 (0.1%) 0/1012 (0%)
    Pleuritic pain 1/1014 (0.1%) 2/1012 (0.2%)
    Pneumonia aspiration 1/1014 (0.1%) 0/1012 (0%)
    Pneumonitis 4/1014 (0.4%) 0/1012 (0%)
    Productive cough 0/1014 (0%) 1/1012 (0.1%)
    Pulmonary artery thrombosis 1/1014 (0.1%) 0/1012 (0%)
    Pulmonary congestion 1/1014 (0.1%) 0/1012 (0%)
    Pulmonary embolism 17/1014 (1.7%) 6/1012 (0.6%)
    Pulmonary hypertension 1/1014 (0.1%) 2/1012 (0.2%)
    Pulmonary mass 0/1014 (0%) 1/1012 (0.1%)
    Pulmonary oedema 3/1014 (0.3%) 2/1012 (0.2%)
    Respiratory failure 3/1014 (0.3%) 4/1012 (0.4%)
    Skin and subcutaneous tissue disorders
    Blister 0/1014 (0%) 1/1012 (0.1%)
    Capillaritis 0/1014 (0%) 1/1012 (0.1%)
    Dermatitis allergic 0/1014 (0%) 1/1012 (0.1%)
    Diabetic foot 0/1014 (0%) 1/1012 (0.1%)
    Erythema 0/1014 (0%) 1/1012 (0.1%)
    Hyperhidrosis 0/1014 (0%) 1/1012 (0.1%)
    Neuropathic ulcer 0/1014 (0%) 1/1012 (0.1%)
    Peau d'orange 1/1014 (0.1%) 0/1012 (0%)
    Skin necrosis 1/1014 (0.1%) 0/1012 (0%)
    Skin oedema 1/1014 (0.1%) 0/1012 (0%)
    Skin ulcer 1/1014 (0.1%) 1/1012 (0.1%)
    Urticaria 1/1014 (0.1%) 1/1012 (0.1%)
    Social circumstances
    Loss of personal independence in daily activities 1/1014 (0.1%) 0/1012 (0%)
    Walking disability 1/1014 (0.1%) 0/1012 (0%)
    Surgical and medical procedures
    Arteriovenous fistula operation 0/1014 (0%) 1/1012 (0.1%)
    Orchidectomy 1/1014 (0.1%) 0/1012 (0%)
    Vascular disorders
    Accelerated hypertension 1/1014 (0.1%) 0/1012 (0%)
    Aortic aneurysm 1/1014 (0.1%) 0/1012 (0%)
    Aortic perforation 0/1014 (0%) 1/1012 (0.1%)
    Arterial stenosis 1/1014 (0.1%) 0/1012 (0%)
    Arterial thrombosis 1/1014 (0.1%) 0/1012 (0%)
    Arteriovenous fistula 1/1014 (0.1%) 1/1012 (0.1%)
    Artery dissection 1/1014 (0.1%) 0/1012 (0%)
    Deep vein thrombosis 20/1014 (2%) 12/1012 (1.2%)
    Embolism venous 1/1014 (0.1%) 0/1012 (0%)
    Haematoma 1/1014 (0.1%) 3/1012 (0.3%)
    Hypertension 2/1014 (0.2%) 6/1012 (0.6%)
    Hypertensive crisis 3/1014 (0.3%) 5/1012 (0.5%)
    Hypertensive emergency 1/1014 (0.1%) 0/1012 (0%)
    Hypotension 3/1014 (0.3%) 8/1012 (0.8%)
    Intermittent claudication 0/1014 (0%) 1/1012 (0.1%)
    Lymphocele 34/1014 (3.4%) 21/1012 (2.1%)
    Lymphorrhoea 3/1014 (0.3%) 0/1012 (0%)
    Malignant hypertension 1/1014 (0.1%) 0/1012 (0%)
    Orthostatic hypotension 0/1014 (0%) 1/1012 (0.1%)
    Pelvic venous thrombosis 0/1014 (0%) 1/1012 (0.1%)
    Peripheral arterial occlusive disease 1/1014 (0.1%) 1/1012 (0.1%)
    Peripheral artery stenosis 0/1014 (0%) 2/1012 (0.2%)
    Peripheral artery thrombosis 2/1014 (0.2%) 1/1012 (0.1%)
    Peripheral ischaemia 2/1014 (0.2%) 1/1012 (0.1%)
    Phlebitis 1/1014 (0.1%) 0/1012 (0%)
    Shock haemorrhagic 1/1014 (0.1%) 2/1012 (0.2%)
    Thrombophlebitis superficial 0/1014 (0%) 1/1012 (0.1%)
    Thrombosis 2/1014 (0.2%) 0/1012 (0%)
    Varicose ulceration 1/1014 (0.1%) 0/1012 (0%)
    Venous stenosis 0/1014 (0%) 1/1012 (0.1%)
    Venous thrombosis 1/1014 (0.1%) 3/1012 (0.3%)
    Venous thrombosis limb 0/1014 (0%) 1/1012 (0.1%)
    Other (Not Including Serious) Adverse Events
    Everolimus Plus@Reduced CNI MPA Plus Standard@CNI
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 951/1014 (93.8%) 942/1012 (93.1%)
    Blood and lymphatic system disorders
    Anaemia 227/1014 (22.4%) 238/1012 (23.5%)
    Leukocytosis 24/1014 (2.4%) 58/1012 (5.7%)
    Leukopenia 94/1014 (9.3%) 194/1012 (19.2%)
    Polycythaemia 52/1014 (5.1%) 42/1012 (4.2%)
    Thrombocytopenia 74/1014 (7.3%) 41/1012 (4.1%)
    Cardiac disorders
    Tachycardia 53/1014 (5.2%) 52/1012 (5.1%)
    Gastrointestinal disorders
    Abdominal pain 94/1014 (9.3%) 104/1012 (10.3%)
    Abdominal pain upper 39/1014 (3.8%) 62/1012 (6.1%)
    Constipation 245/1014 (24.2%) 242/1012 (23.9%)
    Diarrhoea 242/1014 (23.9%) 318/1012 (31.4%)
    Nausea 191/1014 (18.8%) 225/1012 (22.2%)
    Vomiting 120/1014 (11.8%) 140/1012 (13.8%)
    General disorders
    Fatigue 59/1014 (5.8%) 64/1012 (6.3%)
    Oedema peripheral 347/1014 (34.2%) 244/1012 (24.1%)
    Pyrexia 112/1014 (11%) 132/1012 (13%)
    Infections and infestations
    BK virus infection 56/1014 (5.5%) 101/1012 (10%)
    Cytomegalovirus infection 24/1014 (2.4%) 93/1012 (9.2%)
    Nasopharyngitis 110/1014 (10.8%) 117/1012 (11.6%)
    Upper respiratory tract infection 81/1014 (8%) 102/1012 (10.1%)
    Urinary tract infection 219/1014 (21.6%) 249/1012 (24.6%)
    Injury, poisoning and procedural complications
    Complications of transplanted kidney 63/1014 (6.2%) 54/1012 (5.3%)
    Incision site pain 51/1014 (5%) 61/1012 (6%)
    Procedural pain 90/1014 (8.9%) 99/1012 (9.8%)
    Investigations
    Blood creatinine increased 141/1014 (13.9%) 133/1012 (13.1%)
    Weight increased 38/1014 (3.7%) 66/1012 (6.5%)
    Metabolism and nutrition disorders
    Diabetes mellitus 133/1014 (13.1%) 120/1012 (11.9%)
    Dyslipidaemia 98/1014 (9.7%) 57/1012 (5.6%)
    Hypercalcaemia 39/1014 (3.8%) 67/1012 (6.6%)
    Hypercholesterolaemia 103/1014 (10.2%) 61/1012 (6%)
    Hyperglycaemia 140/1014 (13.8%) 144/1012 (14.2%)
    Hyperkalaemia 164/1014 (16.2%) 184/1012 (18.2%)
    Hyperlipidaemia 135/1014 (13.3%) 75/1012 (7.4%)
    Hypertriglyceridaemia 58/1014 (5.7%) 24/1012 (2.4%)
    Hyperuricaemia 49/1014 (4.8%) 64/1012 (6.3%)
    Hypocalcaemia 109/1014 (10.7%) 98/1012 (9.7%)
    Hypokalaemia 148/1014 (14.6%) 87/1012 (8.6%)
    Hypomagnesaemia 134/1014 (13.2%) 168/1012 (16.6%)
    Hypophosphataemia 190/1014 (18.7%) 167/1012 (16.5%)
    Metabolic acidosis 77/1014 (7.6%) 98/1012 (9.7%)
    Vitamin D deficiency 53/1014 (5.2%) 57/1012 (5.6%)
    Musculoskeletal and connective tissue disorders
    Arthralgia 63/1014 (6.2%) 65/1012 (6.4%)
    Back pain 93/1014 (9.2%) 98/1012 (9.7%)
    Pain in extremity 66/1014 (6.5%) 61/1012 (6%)
    Nervous system disorders
    Dizziness 51/1014 (5%) 54/1012 (5.3%)
    Headache 133/1014 (13.1%) 113/1012 (11.2%)
    Tremor 100/1014 (9.9%) 145/1012 (14.3%)
    Psychiatric disorders
    Anxiety 51/1014 (5%) 59/1012 (5.8%)
    Insomnia 100/1014 (9.9%) 138/1012 (13.6%)
    Renal and urinary disorders
    Dysuria 60/1014 (5.9%) 74/1012 (7.3%)
    Haematuria 102/1014 (10.1%) 101/1012 (10%)
    Proteinuria 131/1014 (12.9%) 69/1012 (6.8%)
    Respiratory, thoracic and mediastinal disorders
    Cough 86/1014 (8.5%) 102/1012 (10.1%)
    Dyspnoea 73/1014 (7.2%) 70/1012 (6.9%)
    Skin and subcutaneous tissue disorders
    Acne 56/1014 (5.5%) 37/1012 (3.7%)
    Alopecia 27/1014 (2.7%) 59/1012 (5.8%)
    Vascular disorders
    Hypertension 240/1014 (23.7%) 230/1012 (22.7%)
    Hypotension 62/1014 (6.1%) 78/1012 (7.7%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (ie, data from all sites) in the clinical trial.

    Results Point of Contact

    Name/Title Study Director
    Organization Novartis Pharma
    Phone 8627788300
    Email Novartis.email@novartis.com
    Responsible Party:
    Novartis Pharmaceuticals
    ClinicalTrials.gov Identifier:
    NCT01950819
    Other Study ID Numbers:
    • CRAD001A2433
    • 2013-000322-66
    • NCT02316938
    First Posted:
    Sep 26, 2013
    Last Update Posted:
    Jan 30, 2019
    Last Verified:
    Jan 1, 2019